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2260 diseases found to be fought by fully-activated Vitamin D (Calcitriol) – July 2024

Effects of vitamin D signaling in cardiovascular disease: centrality of macrophage polarization

Front Cardiovasc Med. 2024 Jun 25:11:1388025. doi: 10.3389/fcvm.2024.1388025
Anton Fliri 1, Shama Kajiji 1 founders of Emergent System Analytics

  • "Unlocking the power of proteomics, emergent illuminates a personalized path to health, where precision meets potential, and every individual's unique biology becomes the cornerstone of their well-being."


A small portion of the proteins affected by Calcitriol
Image
Among the leading causes of natural death are cardiovascular diseases, cancer, and respiratory diseases. Factors causing illness include genetic predisposition, aging, stress, chronic inflammation, environmental factors, declining autophagy, and endocrine abnormalities including insufficient vitamin D levels. Inconclusive clinical outcomes of vitamin D supplements in cardiovascular diseases demonstrate the need to identify cause-effect relationships without bias. We employed a spectral clustering methodology capable of analyzing large diverse datasets for examining the role of vitamin D's genomic and non-genomic signaling in disease in this study. The results of this investigation showed the following:

  • (1) vitamin D regulates multiple reciprocal feedback loops including p53, macrophage autophagy, nitric oxide, and redox-signaling;
  • (2) these regulatory schemes are involved in over 2,000 diseases.

Furthermore, the balance between genomic and non-genomic signaling by vitamin D affects autophagy regulation of macrophage polarization in tissue homeostasis. These findings provide a deeper understanding of how interactions between genomic and non-genomic signaling affect vitamin D pharmacology and offer opportunities for increasing the efficacy of vitamin D-centered treatment of cardiovascular disease and healthy lifespans.
 Download the PDF from VitaminDWiki

Additional diseases are probably fought by local (non-liver) generation of Calcitriol

Vitamin D affects 1289+ Genes, but even more proteins (in current study)

342 articles in the Genetics category

see also

Vitamin D blood test misses a lot
in Visio for 2023

  • Vitamin D from coming from tissues (vs blood) was speculated to be 50% in 2014, and by 2017 was speculated to be 90%
  • Note: Good blood test results (> 40 ng) does not mean that a good amount of Vitamin D actually gets to cells
  • A Vitamin D test in cells rather than blood was feasible (2017 personal communication)   Commercially available 2019
    • However, test results would vary in each tissue due to multiple genes
  • Good clues that Vitamin D is being restricted from getting to the cells
    1) A vitamin D-related health problem runs in the family
        especially if it is one of 51+ diseases related to Vitamin D Receptor
    2) Slightly increasing Vitamin D shows benefits (even if conventional Vitamin D test shows an increase)
    3) DNA and VDR tests - 120 to 200 dollars $100 to $250
    4) PTH bottoms out ( shows that parathyroid cells are getting Vitamin d)
       Genes are good, have enough Magnesium, etc.
    5) Back Pain
       probably want at least 2 clues before taking adding vitamin D, Omega-3, Magnesium, Resveratrol, etc
      • The founder of VitaminDWiki took action with clues #3&5
212+ references in the study
  1. Sniderman AD, Furberg CD. Age as a modifiable risk factor for cardiovascular disease. Lancet. (2008) 371:1547-9. https://10.1016/S0140-6736(08)60313-X
  2. Sánchez-Cabo F, Fuster V, Silla-Castro JC, González G, Lorenzo-Vivas E, Alvarez R, et al. Subclinical atherosclerosis and accelerated epigenetic age mediated by inflammation: a multi-omics study. Eur Heart J. (2023) 44(29):2698-709. https://10.1093/eurheartj/ehad361
  3. Spagnoli LG, Bonanno E, Sangiorgi G, Mauriello A. Role of inflammation in atherosclerosis. J Nucl Med. (2007) 48(11):1800-15. https://10.2967/jnumed.107.038661
  4. Ribeiro ASF, Zerolo BE, López-Espuela F, Sánchez R, Fernandes VS. Cardiac system during the aging process. Aging Dis. (2023) 14(4):1105-22. https://10.14336/ AD.2023.0115
  5. North BJ, Sinclair DA. The intersection between aging and cardiovascular disease. Circ Res. (2012) 110(8):1097-108. https://10.1161/CIRCRESAHA.111.246876
  6. Gogulamudi VR, Durrant JR, Adeyemo AO, Ho HM, Walker AE, Lesniewski LA. Advancing age increases the size and severity of spontaneous atheromas in mouse models of atherosclerosis. Geroscience. (2023) 45(3):1913-31. https://10.1007/s11357- 023-00776-8
  7. Boss GR, Seegmiller JE. Age-related physiological changes and their clinical significance. West JMed. (1981) 135(6):434-40. PMID: 7336713; PMCID: PMC1273316
  8. Lv J, Zhang C, Liu X, Gu C, Liu Y, Gao Y, et al. An aging-related immune landscape in the hematopoietic immune system. Immun Ageing. (2024) 21(1):3. https://10.1186/s12979-023-00403-2
  9. Ambale-Venkatesh B, Liu CY, Liu YC, Donekal S, Ohyama Y, Sharma RK, et al. Association of myocardial fibrosis and cardiovascular events: the multi-ethnic study of atherosclerosis. Eur Heart J Cardiovasc Imaging. (2019) 20(2):168-76. https://10.1093/ ehjci/jey140
  10. Meizlish ML, Franklin RA, Zhou X, Medzhitov R. Tissue homeostasis and inflammation. Annu Rev Immunol. (2021) 39:557-81. https://10.1146/annurev- immunol-061020-053734
  11. Hu H, Cheng X, Li F, Guan Z, Xu J, Wu D, et al. Defective efferocytosis by aged macrophages promotes STING signaling mediated inflammatory liver injury. Cell Death Discov. (2023) 9(1):236. https://10.1038/s41420-023-01497-9
  12. Zhong W, Rao Z, Xu J, Sun Y, Hu H, Wang P, et al. Defective mitophagy in aged macrophages promotes mitochondrial DNA cytosolic leakage to activate STING signaling during liver sterile inflammation. Aging Cell. (2022) 21(6):e13622. https://10.1111/acel.13622
  13. Tran M, Reddy PH. Defective autophagy and mitophagy in aging and Alzheimer’s disease. Front Neurosci. (2021) 14:612757. https://10.3389/fnins.2020. 612757
  14. Gladyshev VN, Kritchevsky SB, Clarke SG, Cuervo AM, Fiehn O, de Magalhâes JP, et al. Molecular damage in aging. Nat Aging. (2021) 1(12):1096-106. https://10.1038/ s43587-021-00150-3
  15. Zhang Z, Guo Q, Zhao Z, Nie M, Shi Q, Li E, et al. DNMT3B activates FGFR3- mediated endoplasmic reticulum stress by regulating PTPN2 promoter methylation to promote the development of atherosclerosis. FASEB J. (2023) 37(8):e23085. https://10.1096/fj.202300665R
  16. Jones L, Passegue E. Stem cells homeostasis and aging. Innov Aging. (2023) 7 (Suppl 1):259-60. https://10.1093/geroni/igad104.0862
  17. Li Y, Li Q, Fan GC. Macrophage efferocytosis in cardiac pathophysiology and repair. Shock. (2021) 55(2):177-88. https://10.1097/SHK.0000000000001625
  18. van den Beld AW, Kaufman JM, Zillikens MC, Lamberts SWJ, Egan JM, van der Lely AJ. The physiology of endocrine systems with ageing. Lancet Diabetes Endocrinol. (2018) 6(8):647-58. https://10.1016/S2213-8587(18)30026-3
  19. Cookson MR. Aging-RNA in development and disease. Wiley Interdiscip Rev RNA. (2012) 3(1):133-43. https://10.1002/wrna.109
  20. Smit V, de Mol J, Schaftenaar FH, Depuydt MAC, Postel RJ, Smeets D, et al. Single-cell profiling reveals age-associated immunity in atherosclerosis. Cardiovasc Res. (2023) 119(15):2508-21. https://10.1093/cvr/cvad099
  21. Popa-Fotea NM, Ferdoschi CE, Micheu MM. Molecular and cellular mechanisms of inflammation in atherosclerosis. Front Cardiovasc Med. (2023) 10:1200341. https://10.3389/fcvm.2023.1200341
  22. Vidak S, Serebryannyy LA, Pegoraro G, Misteli T. Activation of endoplasmic reticulum stress in premature aging via the inner nuclear membrane protein SUN2. Cell Rep. (2023) 42(5):112534. https://10.1016/j.celrep.2023.112534
  23. Zhang K, Kaufman RJ. From endoplasmic-reticulum stress to the inflammatory response. Nature. (2008) 454(7203):455-62. https://10.1038/nature07203
  24. Lopez DV, Al-Jaberi FAH, Woetmann A, 0dum N, Bonefeld CM, Kongsbak- Wismann M, et al. macrophages control the bioavailability of vitamin D and vitamin D-regulated T cell responses. Front Immunol. (2021) 12:722806. https://10.3389/fimmu.2021.722806
  25. Sendama W. The effect of ageing on the resolution of inflammation. Ageing Res Rev. (2020) 57:101000. https://10.1016/j.arr.2019.101000
  26. Rochette L, Dogon G, Rigal E, Zeller M, Cottin Y, Vergely C. Interplay between efferocytosis and atherosclerosis. Arch Cardiovasc Dis. (2023) 116(10):474-84. https://10.1016/j.acvd.2023.07.007
  27. Guo J, Huang X, Dou L, Yan M, Shen T, Tang W, et al. Aging and aging-related diseases: from molecular mechanisms to interventions and treatments. Signal Transduct Target Ther. (2022) 7(1):391. https://10.1038/s41392-022-01251-0
  28. Malainou C, Abdin SM, Lachmann N, Matt U, Herold S. Alveolar macrophages in tissue homeostasis, inflammation, and infection: evolving concepts of therapeutic targeting. J Clin Invest. (2023) 133(19):e170501. https://10.1172/JCI170501
  29. Kojima Y, Weissman IL, Leeper NJ. The role of efferocytosis in atherosclerosis. Circulation. (2017) 135(5):476-89. https://10.1161/CIRCULATIONAHA.116.025684
  30. Xie L, Chen J, Wang Y, Jin C, Xie Y, Ma H, et al. Emerging roles of macrophages in heart failure and associated treatment approaches. Ther Adv Chronic Dis. (2023) 14:20406223231168755. https://10.1177/20406223231168755
  31. Malik JA, Zafar MA, Lamba T, Nanda S, Khan MA, Agrewala JN. The impact of aging-induced gut microbiome dysbiosis on dendritic cells and lung diseases. Gut Microbes. (2023) 15(2):2290643. https://10.1080/19490976.2023.2290643
  32. Suwa Y, Nagafuchi Y, Yamada S, Fujio K. The role of dendritic cells and their immunometabolism in rheumatoid arthritis. Front Immunol. (2023) 14:1161148. https://10.3389/fimmu.2023.1161148
  33. Ahmed AS, Sheng MH, Wasnik S, Baylink DJ, Lau KW. Effect of aging on stem cells. World J Exp Med. (2017) 7(1):1—10.https://10.5493/wjem.v7.i1.1
  34. Wang H, Chen W, Li D, Yin X, Zhang X, Olsen N, et al. vitamin D and chronic diseases. AgingDis. (2017) 8(3):346-53. https://10.14336/AD.2016.1021
  35. Khammissa RAG, Fourie J, Motswaledi MH, Ballyram R, Lemmer J, Feller L. The biological activities of vitamin D and its receptor in relation to calcium and bone homeostasis, cancer, immune and cardiovascular systems, skin biology, and oral health. Biomed Res Int. (2018) 2018:9276380. https://10.1155/2018/9276380
  36. Shi H, Duan J, Wang J, Li H, Wu Z, Wang S, et al. 1,25(OH)2D3 promotes macrophage efferocytosis partly by upregulating ASAP2 transcription via the VDR- bound enhancer region and ASAP2 may affect antiviral immunity. Nutrients. (2022) 14(22):4935. https://10.3390/nu14224935
  37. Oh J, Riek AE, Darwech I, Funai K, Shao J, Chin K, et al. Deletion of macrophage vitamin D receptor promotes insulin resistance and monocyte cholesterol transport to accelerate atherosclerosis in mice. Cell Rep. (2015) 10 (11):1872-86. https://10.1016/j.celrep.2015.02.043
  38. Kumar S, Nanduri R, Bhagyaraj E, Kalra R, Ahuja N, Chacko AP, et al. vitamin D3-VDR-PTPN6 axis mediated autophagy contributes to the inhibition of macrophage foam cell formation. autophagy. (2021) 17(9):2273-89. https://10.1080/ 15548627.2020.1822088
  39. Thompson B, Waterhouse M, English DR, McLeod DS, Armstrong BK, Baxter C, et al. vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial. BMJ. (2023) 381:e075230. https://10.1136/bmj-2023-075230
  40. Manolis AA, Manolis TA, Melita H, Manolis AS. Role of vitamins in cardiovascular health: know your facts-part 2. Curr Vasc Pharmacol. (2023) 21 (6):399-423. https://10.2174/1570161121666230911115725
  41. Patriota P, Guessous I, Rezzi S, Marques-Vidal P. vitamin D levels are associated with cardiovascular disease events but not with cardiovascular disease or overall mortality: a prospective population-based study. Nutrients. (2023) 15(18):4046. https://10.3390/nu15184046
  42. Cassard SD, Fitzgerald KC, Qian P, Emrich SA, Azevedo CJ, Goodman AD, et al. High-dose vitamin D3 supplementation in relapsing-remitting multiple sclerosis: a randomised clinical trial. EClinicalMedicine. (2023) 59:101957. https://10.1016/j.eclinm. 2023.101957
  43. Tobias DK, Luttmann-Gibson H, Mora S, Danik J, Bubes V, Copeland T, et al. Association of body weight with response to vitamin D supplementation and metabolism. JAMA Netw Open. (2023) 6(1):e2250 doi:10.1001/jamanetworkopen.2022.50681
  44. Anton FF, Shama K. vitamin D deficiency-associated comorbidities: a protein network dynamics perspective. Med. Res. Archives. (2023) 11(6):2023. https://10.18103/ mra.v11i6.3996
  45. Fliri AF, Loging WT, Volkmann RA. Analysis of information flows in interaction networks: implication for drug discovery and pharmacological research. Discov Med. (2011) 11(57):133-43. PMID: 21356168
  46. Fliri AF, Loging WT, Volkmann RA. Drug effects viewed from a signal transduction network perspective. J Med Chem. (2009) 52(24):8038-46. https://10.1021/jm901001p
  47. Fliri AF, Kajiji S. Functional characterization of nutraceuticals using spectral clustering: centrality of caveolae-mediated endocytosis for management of nitric oxide and vitamin D deficiencies and atherosclerosis. Front Nutr. (2022) 9:885364. https://10.3389/fnut.2022.885364
  48. Fierro-Monti I, Wright JC, Choudhary JS, Vizcaíno JA. Identifying individuals using proteomics: are we there yet? Front Mol Biosci. (2022 Nov 29) 9:1062031. https://10.3389/fmolb.2022.1062031
  49. Zhu X, Shen X, Qu J, Straubinger RM, Jusko WJ. Multi-scale network model supported by proteomics for analysis of combined gemcitabine and birinapant effects in pancreatic cancer cells. CPT Pharmacometrics Syst Pharmacol. (2018 Sep) 7(9):549-61. https://10.1002/psp4.12320
  50. Kustatscher G, Collins T, Gingras AC, Guo T, Hermjakob H, Ideker T, et al. Understudied proteins: opportunities and challenges for functional proteomics. Nat Methods. (2022) 19(7):774-9. https://10.1038/s41592-022-01454-x
  51. Ivanov PC, Bartsch RP. Network physiology: mapping interactions between networks of physiologic networks. In: D’Angostino G, Scala A, editors. Networks of Networks: The Last Frontier of Complexity. Cham: Springer (2014). p. 203-22.
  52. Broido AD, Clauset A. Scale-free networks are rare. Nat Commun. (2019) 10:1017. https://10.1038/s41467-019-08746-5
  53. Woessmann J, Kotol D, Hober A, Uhlen M, Edfors F. Addressing the protease bias in quantitative proteomics. J Proteome Res. (2022 Oct 7) 21(10):2526-34. https://10.1021/acs.jproteome.2c00491
  54. Bantscheff M, Schirle M, Sweetman G, Rick J, Kuster B. Quantitative mass spectrometry in proteomics: a critical review. Anal Bioanal Chem. (2007) 389 (4):1017-31. https://10.1007/s00216-007-1486-6
  55. Szklarczyk D, Gable AL, Nastou KC, Lyon D, Kirsch R, Pyysalo S, et al. The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. (2021) 49(D1):D605-12. https://10.1093/nar/gkaa1074
  56. Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P, Mardinoglu A, et al. proteomics. Tissue-based map of the human proteome. Science. (2015) 347 (6220):1260419. https://10.1126/science.1260419
  57. National Center for Biotechnology Information (NCBI). Bethesda, MD: National Library of Medicine (US), National Center for Biotechnology Information (1988). Available online at: https://www.ncbi.nlm.nih.gov/ (cited April 06, 2017).
  58. TIBCO Statistica, v. 13.3.0, TIBCO Software Inc, Palo Alto, CA, USA (2017). https://www.tibco.com/products/tibco-statistica (Accessed December 20, 2023).
  59. Fliri AF, Loging WT, Volkmann RA. Cause-effect relationships in medicine: a protein network perspective. Trends Pharmacol Sci. (2010) 31(11):547-55. https://10.1016/j.tips.2010.07.005
  60. Dunn K, Marshall JG, Wells AL, Backus JEB. Examining the role of MEDLINE as a patient care information resource: an analysis of data from the Value of Libraries study. J Med Libr Assoc. (2017 Oct) 105(4):336-46. https://10.5195/jmla.2017.87
  61. Finlayson SG, LePendu P, Shah NH. Building the graph of medicine from millions of clinical narratives. Sci Data. (2014 Sep 16) 1:140032. https://10.1038/sdata.2014.32
  62. Szklarczyk D, Franceschini A, Kuhn M, Simonovic M, Roth A, Minguez P, et al. The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res. (2011) 39(Database issue):D561-8. https://10.1093/nar/gkq973
  63. Kaushal D, Naeve CW. An overview of spotfire for gene-expression studies. Curr Protoc Hum Genet. (2005) 45(1):11.9.1-21. https://10.1002/0471142905.hg1109s45
  64. Della Nera G, Sabatino L, Gaggini M, Gorini F, Vassalle C. vitamin D determinants, status, and antioxidant/anti-inflammatory-related effects in cardiovascular risk and disease: not the last word in the controversy. Antioxidants (Basel). (2023) 12(4):948. https://10.3390/antiox12040948
  65. Daryabor G, Gholijani N, Kahmini FR. A review of the critical role of vitamin D axis on the immune system. Exp Mol Pathol. (2023) 132-133:104866. https://10.1016/j. yexmp.2023.104866
  66. Gaucci E, Raimondo D, Grillo C, Cervoni L, Altieri F, Nittari G, et al. Analysis of the interaction of calcitriol with the disulfide isomerase ERp57. Sci Rep. (2016) 6:37957. https://10.1038/srep37957
  67. Zmijewski MA. Nongenomic activities of vitamin D. Nutrients. (2022) 14 (23):5104. https://10.3390/nu14235104
  68. Nowak JI, Olszewska AM, Piotrowska A, Myszczynski K, Domzalski P, Zmijewski MA. PDIA3 modulates genomic response to 1,25-dihydroxyvitamin D3 in squamous cell carcinoma of the skin. Steroids. (2023) 199:109288. https://10.1016/j. steroids.2023.109288
  69. Tu Z, Ouyang Q, Long X, Wu L, Li J, Zhu X, et al. protein disulfide-isomerase A3 is a robust prognostic biomarker for cancers and predicts the immunotherapy response effectively. Front. Immunol. (2022) 2022(13):837512. https://10.3389/fimmu.2022.837512
  70. Zhao G, Lu H, Li C. Proapoptotic activities of protein disulfide isomerase (PDI) and PDIA3 protein, a role of the bcl-2 protein bak. J Biol Chem. (2015) 290 (14):8949-63. https://10.1074/jbc.M114.619353
  71. Cockram TOJ, Dundee JM, Popescu AS, Brown GC. The phagocytic code regulating phagocytosis of mammalian cells. Front Immunol. (2021) 12:629979. https://10.3389/fimmu.2021.629979
  72. Keasey MP, Razskazovskiy V, Jia C, Peterknecht ED, Bradshaw PC, Hagg T. PDIA3 Inhibits mitochondrial respiratory function in brain endothelial cells and C. elegans through STAT3 signaling and decreases survival after OGD. Cell Commun Signal. (2021) 19(1):119. https://10.1186/s12964-021-00794-z
  73. Xiao Y, Li C, Gu M, Wang H, Chen W, Luo G, et al. protein disulfide isomerase silence inhibits inflammatory functions of macrophages by suppressing reactive oxygen species and NF-kB pathway. Inflammation. (2018) 41(2):614-25. https://10.1007/ s10753-017-0717-z
  74. Pol JG, Plantureux C, Pérez-Lanzón M, Kroemer G. PDIA3 as a potential bridge between immunogenic cell death and autoreactivity. Oncoimmunology. (2022) 11:2130558. https://10.1080/2162402X.2022.2130558
  75. Barragan M, Good M, Kolls JK. Regulation of dendritic cell function by vitamin D. Nutrients. (2015) 7(9):8127-51. https://10.3390/nu7095383
  76. Huang T, You Q, Huang D, Zhang Y, He Z, Shen X, et al. A positive feedback between PDIA3P1 and OCT4 promotes the cancer stem cell properties of esophageal squamous cell carcinoma. Cell Commun Signal. (2024) 22(1):60. https://10.1186/s12964- 024-01475-3
  77. Liu Y, Zhao X, Jian J, Hasan S, Liu C. Interaction with ERp57 is required for progranulin protection against type 2 Gaucher disease. Biosci Trends. (2023) 17(1) :126-35. https://10.5582/bst.2023.01022
  78. Zmijewski MA, Carlberg C. vitamin D receptor(s): in the nucleus but also at membranes? Exp Dermatol. (2020) 29(9):876-84. https://10.1111/exd.14147
  79. Fliri AF, Loging WT, Thadeio PF, Volkmann RA. Biospectra analysis: model proteome characterizations for linking molecular structure and biological response. J Med Chem. (2005) 48(22):6918-25. https://10.1021/jm050494g
  80. Ivashkiv LB, Park SH. Epigenetic regulation of myeloid cells. Microbiol Spectr. (2016) 4(3):1-29. https://10.1128/microbiolspec.MCHD-0010-2015
  81. Català-Moll F, Ferreté-Bonastre AG, Godoy-Tena G, Morante-Palacios O, Ciudad L, Barberà L, et al. vitamin D receptor, STAT3, and TET2 cooperate to establish tolerogenesis. Cell Rep. (2022) 38(3):110244. https://10.1016/j.celrep.2021. 110244
  82. Vasudevan D, Bovee RC, Thomas DD. Nitric oxide, the new architect of epigenetic landscapes. Nitric Oxide. (2016) 59:54-62. https://10.1016/j.niox.2016.08.002
  83. Berridge MJ. vitamin D, reactive oxygen species and calcium signalling in ageing and disease. Philos Trans R Soc Lond B Biol Sci. (2016) 371(1700):20150434. https://10.1098/rstb.2015.0434
  84. Fetahu IS, Hobaus J, Kállay E. vitamin D and the epigenome. Front Physiol. (2014) 5:164. https://10.3389/fphys.2014.00164
  85. Hossain S, Liu Z, Wood RJ. Histone deacetylase activity and vitamin D- dependent gene expressions in relation to sulforaphane in human breast cancer cells. J Food Biochem. (2020) 44(2):e13114. https://10.1111/jfbc.13114
  86. Fliri AF, Loging WT, Thadeio PF, Volkmann RA. Biological spectra analysis: linking biological activity profiles to molecular structure. Proc Natl Acad Sci USA. (2005) 102(2):261-6. https://10.1073/pnas.0407790101
  87. Baraniecki L, Tokarz-Deptula B, Syrenicz A, Deptula W. Macrophage efferocytosis in atherosclerosis. Scand J Immunol. (2023) 97(5):e13251. https://10.1111/ sji.13251
  88. Sergin I, Razani B. Self-eating in the plaque: what macrophage autophagy reveals about atherosclerosis. Trends Endocrinol Metab. (2014) 25(5):225-34. https://10.1016/j. tem.2014.03.010
  89. Ni D, Mo Z, Yi G. Recent insights into atherosclerotic plaque cell autophagy. Exp Biol Med (Maywood). (2021) 246(24):2553-8. https://10.1177/15353702211038894
  90. Shao BZ, Han BZ, Zeng YX, Su DF, Liu C. The roles of macrophage autophagy in atherosclerosis. Acta Pharmacol Sin. (2016) 37(2):150-6. https://10.1038/aps.2015.87
  91. Hou P, Fang J, Liu Z, Shi Y, Agostini M, Bernassola F, et al. Macrophage polarization and metabolism in atherosclerosis. Cell Death Dis. (2023) 14(10):691. https://10.1038/s41419-023-06206-z
  92. Yang S, Yuan HQ, Hao YM, Ren Z, Qu SL, Liu LS, et al. Macrophage polarization in atherosclerosis. Clin Chim Acta. (2020) 501:142-6. https://10.1016/j.cca. 2019.10.034
  93. Molnár AÁ, Pásztor DT, Tarcza Z, Merkely B. Cells in atherosclerosis: focus on cellular senescence from basic science to clinical practice. Int J Mol Sci. (2023) 24 (24):17129. https://10.3390/ijms242417129
  94. Yang S, Wu M, Li X, Zhao R, Zhao Y, Liu L, et al. Role of endoplasmic reticulum stress in atherosclerosis and its potential as a therapeutic target. Oxid Med Cell Longev. (2020) 2020:9270107. https://10.1155/2020/9270107
  95. Immanuel J, Yun S. Vascular inflammatory diseases and endothelial phenotypes. Cells. (2023) 12(12):1640. https://10.3390/cells12121640
  96. Aronova A, Tosato F, Naser N, Asare Y. Innate immune pathways in atherosclerosis-from signaling to long-term epigenetic reprogramming. Cells. (2023) 12(19):2359. https://10.3390/cells12192359
  97. Shu Y, Jin S. Caveolin-1 in endothelial cells: a potential therapeutic target for atherosclerosis. Heliyon. (2023) 9(8):e18653. https://10.1016/j.heliyon.2023.e18653
  98. Kockx MM, Herman AG. Apoptosis in atherosclerosis: beneficial or detrimental? CardiovascRes. (2000) 45(3):736-46. https://10.1016/s0008-6363(99)00235-7
  99. Shafi O. Switching of vascular cells towards atherogenesis, and other factors contributing to atherosclerosis: a systematic review. Thromb J. (2020) 18:28. https://10.1186/s12959-020-00240-z
  100. Ferreira-Martins AJ, Castaldoni R, Alencar BM, Ferreira MV, Nogueira T, Rios RA, et al. Full-scale network analysis reveals properties of the FV protein structure organization. Sci Rep. (2023) 13(1):9546. https://10.1038/s41598-023-36528-z
  101. Wojtasinska A, Frçk W, Lisinska W, Sapeda N, Mlynarska E, Rysz J, et al. Novel insights into the molecular mechanisms of atherosclerosis. Int J Mol Sci. (2023) 24 (17):13434. https://10.3390/ijms241713434
  102. Weber C, Habenicht AJR, von Hundelshausen P. Novel mechanisms and therapeutic targets in atherosclerosis: inflammation and beyond. Eur Heart J. (2023) 44(29):2672-81. https://10.1093/eurheartj/ehad304
  103. Böger RH, Bode-Böger SM, Frölich JC. The L-arginine-nitric oxide pathway: role in atherosclerosis and therapeutic implications. atherosclerosis. (1996) 127 (1):1—11. https://10.1016/s0021-9150(96)05953-9
  104. Madamanchi NR, Runge MS. Redox signaling in cardiovascular health and disease. Free Radic Biol Med. (2013) 61:473-501. https://10.1016/j.freeradbiomed.2013. 04.001
  105. Saccone D, Asani F, Bornman L. Regulation of the vitamin D receptor gene by environment, genetics and epigenetics. Gene. (2015) 561(2):171-80. https://10.1016/j. gene.2015.02.024
  106. Ho SM, Johnson A, Tarapore P, Janakiram V, Zhang X, Leung YK. Environmental epigenetics and its implication on disease risk and health outcomes published correction appears in ILAR J. 2017 Dec 15;58(3):413. ILAR J. (2012) 53 (3-4):289-305. https://10.1093/ilar.53.3-4.289
  107. Lee HT, Oh S, Ro DH, Yoo H, Kwon YW. The key role of DNA methylation and histone acetylation in epigenetics of atherosclerosis. J Lipid Atheroscler. (2020) 9 (1) :419-34. https://10.12997/jla.2020.9.3.419
  108. Bruunsgaard H, Skinhoj P, Pedersen AN, Schroll M, Pedersen BK. Ageing, tumour necrosis factor-alpha (TNF-alpha) and atherosclerosis. Clin Exp Immunol. (2000) 121(2):255-60. https://10.1046/j.1365-2249.2000.01281.x
  109. Gomez-Bernal F, Quevedo-Abeledo JC, Garcia-Gonzalez M, Fernandez- Cladera Y, Gonzalez-Rivero AF, Martin-Gonzalez C, et al. Transforming growth factor beta 1 is associated with subclinical carotid atherosclerosis in patients with systemic lupus erythematosus. Arthritis Res Ther. (2023) 25(1):64. https://10.1186/ s13075-023-03046-2
  110. Proctor BM, Ren J, Chen Z, Schneider JG, Coleman T, Lupu TS, et al. Grb2 is required for atherosclerotic lesion formation. Arterioscler Thromb Vasc Biol. (2007) 27 (6):1361-7. https://10.1161/ATVBAHA.106.134007
  111. Gaddis DE, Padgett LE, Wu R, Hedrick CC. Neuropilin-1 expression on CD4T cells is atherogenic and facilitates T cell migration to the aorta in atherosclerosis. J Immunol. (2019) 203(12):3237-46. https://10.4049/jimmunol.1900245
  112. Suarez-Rivero JM, Pastor-Maldonado CJ, Povea-Cabello S, Âlvarez-Cordoba
  113. M, Villalon-Garcia I, Talaveron-Rey M, et al. From mitochondria to atherosclerosis: the inflammation path. Biomedicines. (2021) 9(3):258. doi: 10.3390/biomedicines9030258
  114. Poznyak AV, Sukhorukov VN, Zhuravlev A, Orekhov NA, Kalmykov V, Orekhov AN. Modulating mTOR signaling as a promising therapeutic strategy for atherosclerosis. Int J Mol Sci. (2022) 23(3):1153. https://10.3390/ijms23031153
  115. Zhang Q, Wen XH, Tang SL, Zhao ZW, Tang CK. Role and therapeutic potential of gelsolin in atherosclerosis. J Mol Cell Cardiol. (2023) 178:59-67. https://10.1016/j.yjmcc.2023.03.012
  116. Gunasekar P, Swier VJ, Fleegel JP, Boosani CS, Radwan MM, Agrawal DK. vitamin D and macrophage polarization in epicardial adipose tissue of atherosclerotic swine. PLoS One. (2018) 13(10):e0199411. https://10.1371/journal.pone. 019941
  117. Oeckinghaus A, Ghosh S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol. (2009) 1(4):a000034. https://10.1101/ cshperspect.a000034
  118. Wang EJ, Wu MY, Ren ZY, Zheng Y, Ye RD, Tan CSH, et al. Targeting macrophage autophagy for inflammation resolution and tissue repair in inflammatory bowel disease. Burns Trauma. (2023) 11:tkad004. https://10.1093/burnst/tkad004
  119. Mallat Z, Corbaz A, Scoazec A, Besnard S, Lesèche G, Chvatchko Y, et al. Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability. Circulation. (2001) 104(14):1598-603. https://10.1161/hc3901.096721
  120. Chu T, Xu X, Ruan Z, Wu L, Zhou M, Zhu G. miR-146a contributes to atherosclerotic plaque stability by regulating the expression of TRAF6 and IRAK-1. Mol Biol Rep. (2022) 49(6):4205-16. https://10.1007/s11033-022-07253-z
  121. Fei J, Sun Y, Duan Y, Xia J, Yu S, Ouyang P, et al. Low concentration of rutin treatment might alleviate the cardiotoxicity effect of pirarubicin on cardiomyocytes via activation of PI3 K/AKT/mTOR signaling pathway. Biosci Rep. (2019) 39(6): BSR20190546. https://10.1042/BSR20190546
  122. Ma C, Lu T, He Y, Guo D, Duan L, Jia R, et al. Comprehensive analysis of autophagy-related gene expression profiles identified five gene biomarkers associated with immune infiltration and advanced plaques in carotid atherosclerosis. Orphanet J Rare Dis. (2023) 18(1):66. https://10.1186/s13023-023-02660-2
  123. Perrotta I, Aquila S. The role of oxidative stress and autophagy in atherosclerosis. Oxid Med Cell Longev. (2015) 2015:130315. https://10.1155/2015/130315
  124. Wu CM, Zheng L, Wang Q, Hu YW. The emerging role of cell senescence in atherosclerosis. Clin Chem Lab Med. (2020) 59(1):27—38. https://10.1515/cclm- 2020-0601
  125. Grootaert MOJ, Moulis M, Roth L, Martinet W, Vindis C, Bennett MR, et al. Vascular smooth muscle cell death, autophagy and senescence in atherosclerosis. Cardiovasc Res. (2018) 114(4):622-34. https://10.1093/cvr/cvy007
  126. Xu S, Lyu QR, Ilyas I, Tian XY, Weng J. Vascular homeostasis in atherosclerosis: a holistic overview. Front Immunol. (2022) 13:976722. https://10.3389/ fimmu.2022.976722
  127. Yamagishi N, Ueda T, Mori A, Saito Y, Hatayama T. Decreased expression of endoplasmic reticulum chaperone GRP78 in liver of diabetic mice. Biochem Biophys Res Commun. (2012) 417(1):364-70. https://10.1016/j.bbrc.2011.11.118
  128. Liu J, Xu K, Chase M, Ji Y, Logan JK, Buchsbaum RJ. Tiam1-regulated osteopontin in senescent fibroblasts contributes to the migration and invasion of associated epithelial cells. J Cell Sci. (2012) 125(Pt 2):376-86. https://10.1242/jcs.089466
  129. Wolak T. Osteopontin—a multi-modal marker and mediator in atherosclerotic vascular disease. atherosclerosis. (2014) 236(2):327-37. https://10.1016/j.atherosclerosis. 2014.07.004
  130. Li M, Jiao Q, Xin W, Niu S, Liu M, Song Y, et al. Corrigendum: the emerging role of rho guanine nucleotide exchange factors in cardiovascular disorders: insights into atherosclerosis: a mini review. Front Cardiovasc Med. (2022) 9:850258. https://10.3389/fcvm.2022.850258. Erratum for: Front Cardiovasc Med. 2022 Jan 03;8:782098.
  131. Moon SY, Shin SA, Oh YS, Park HH, Lee CS. Understanding the role of the BAI subfamily of adhesion G protein-coupled receptors (GPCRs) in pathological and physiological conditions. Genes (Basel). (2018) 9(12):597. https://10.3390/genes9120597
  132. Thorp E, Cui D, Schrijvers DM, Kuriakose G, Tabas I. Mertk receptor mutation reduces efferocytosis efficiency and promotes apoptotic cell accumulation and plaque necrosis in atherosclerotic lesions of apoe-/- mice. Arterioscler Thromb Vasc Biol. (2008) 28(8):1421-8. https://10.1161/ATVBAHA.108.167197
  133. Liao X, Sluimer JC, Wang Y, Subramanian M, Brown K, Pattison JS, et al. Macrophage autophagy plays a protective role in advanced atherosclerosis. Cell Metab. (2012) 15(4):545-53. https://10.1016/j.cmet.2012.01.022
  134. Galic M, Tsai FC, Collins SR, Matis M, Bandara S, Meyer T. Dynamic recruitment of the curvature-sensitive protein ArhGAP44 to nanoscale membrane deformations limits exploratory filopodia initiation in neurons. Elife. (2014) 3: e03116. https://10.7554/eLife.03116
  135. Abou-Kheir W, Isaac B, Yamaguchi H, Cox D. Membrane targeting of WAVE2 is not sufficient for WAVE2-dependent actin polymerization: a role for IRSp53 in mediating the interaction between Rac and WAVE2. J Cell Sci. (2008) 121(Pt 3):379-90. https://10.1242/jcs.010272
  136. Singh RK, Haka AS, Bhardwaj P, Zha X, Maxfield FR. Dynamic actin reorganization and vav/Cdc42-dependent actin polymerization promote macrophage aggregated LDL (low-density lipoprotein) uptake and catabolism. Arterioscler Thromb Vasc Biol. (2019) 39(2):137-49. https://10.1161/ATVBAHA.118.312087
  137. Nakagawa H, Miki H, Nozumi M, Takenawa T, Miyamoto S, Wehland J, et al. IRSp53 is colocalised with WAVE2 at the tips of protruding lamellipodia and filopodia independently of Mena. J Cell Sci. (2003) 116(Pt 12):2577-83. https://10.1242/jcs.00462
  138. Ding B, Yang S, Schaks M, Liu Y, Brown AJ, Rottner K, et al. Structures reveal a key mechanism of WAVE regulatory complex activation by Rac1 GTPase. Nat Commun. (2022) 13(1):5444. https://10.1038/s41467-022-33174-3
  139. Kramer DA, Piper HK, Chen B. WASP family proteins: molecular mechanisms and implications in human disease published correction appears in Eur J Cell Biol. 2023 Mar;102(1):151287. Eur J Cell Biol. (2022) 101(3):151244. https://10.1016/j.ejcb. 2022.151244
  140. Chen B, Brinkmann K, Chen Z, Pak CW, Liao Y, Shi S, et al. The WAVE regulatory complex links diverse receptors to the actin cytoskeleton. Cell. (2014) 156 (1-2):195-207. https://10.1016/j.cell.2013.11.048
  141. Lim KB, Bu W, Goh WI, Koh E, Ong SH, Pawson T, et al. The Cdc42 effector IRSp53 generates filopodia by coupling membrane protrusion with actin dynamics. J Biol Chem. (2008) 283(29):20454-72. https://10.1074/jbc.M710185200
  142. Cai GQ, Chou CF, Hu M, Zheng A, Reichardt LF, Guan JL, et al. Neuronal Wiskott-Aldrich syndrome protein (N-WASP) is critical for formation of a-smooth muscle actin filaments during myofibroblast differentiation. Am J Physiol Lung Cell Mol Physiol. (2012) 303(8):L692-702. https://10.1152/ajplung.00390.2011
  143. Chen H, Reed G, Guardia J, Lakhan S, Couture O, Hays E, et al. vitamin D directly regulates Mdm2 gene expression in osteoblasts. Biochem Biophys Res Commun. (2013) 430(1):370-4. https://10.1016/j.bbrc.2012.11.003
  144. Wu X, Bayle JH, Olson D, Levine AJ. The p53-mdm-2 autoregulatory feedback loop. Genes Dev. (1993) 7(7A):1126-32. https://10.1101/gad.7.7a.1126
  145. Moon SH, Huang CH, Houlihan SL, Regunath K, Freed-Pastor WA, Morris JP 4th, et al. p53 represses the mevalonate pathway to mediate tumor suppression. Cell. (2019) 176(3):564-580.e19. https://10.1016/j.cell.2018.11.011
  146. Dong B, Wu M, Li H, Kraemer FB, Adeli K, Seidah NG, et al. Strong induction of PCSK9 gene expression through HNF1alpha and SREBP2: mechanism for the resistance to LDL-cholesterol lowering effect of statins in dyslipidemic hamsters. J Lipid Res. (2010) 51(6):1486-95. https://10.1194/jlr.M003566
  147. Forrester K, Ambs S, Lupold SE, Kapust RB, Spillare EA, Weinberg WC, et al. Nitric oxide-induced p53 accumulation and regulation of inducible nitric oxide synthase expression by wild-type p53. Proc Natl Acad Sci USA. (1996) 93 (6):2442-7. https://10.1073/pnas.93.6.2442
  148. Ambs S, Ogunfusika MO, Merriam WG, Bennett WP, Billiar TR, Harris CC. Up- regulation of inducible nitric oxide synthase expression in cancer-prone p53 knockout mice. Proc Natl Acad Sci USA. (1998) 95(15):8823-8. https://10.1073/pnas.95.15.882
  149. Chan GH, Chan E, Kwok CT, Leung GP, Lee SM, Seto SW. The role of p53 in the alternation of vascular functions. Front Pharmacol. (2022) 13:981152. https://10.3389/fphar.2022.981152
  150. Jansson M, Durant ST, Cho EC, Sheahan S, Edelmann M, Kessler B, et al. Arginine methylation regulates the p53 response. Nat Cell Biol. (2008) 10 (12):1431-9. https://10.1038/ncb1802
  151. Heyne K, Heil TC, Bette B, Reichrath J, Roemer K. MDM2 binds and inhibits vitamin D receptor__. Cell Cycle. (2015) 14(13):2003-10.https://10.1080/15384101.2015. 104417
  152. Zhao Y, Yu H, Hu W. The regulation of MDM2 oncogene and its impact on human cancers. Acta Biochim Biophys Sin (Shanghai). (2014) 46(3):180-9. https://10.1093/abbs/gmt147
  153. Rohe B, Safford SE, Nemere I, Farach-Carson MC. Regulation of expression of 1,25D3-MARRS/ERp57/PDIA3 in rat IEC-6 cells by TGF beta and 1,25(OH)2D3. Steroids. (2007) 72(2):144-50. https://10.1016/j.steroids.2006.11.013
  154. Srikuea R, Hirunsai M. TGF-p1 stimulation and VDR-dependent activation modulate calcitriol action on skeletal muscle fibroblasts and Smad signalling- associated fibrogenesis. Sci Rep. (2023) 13(1):13811. https://10.1038/s41598-023- 40978-w
  155. Meek DW, Anderson CW. Posttranslational modification of p53: cooperative integrators of function. Cold Spring Harb Perspect Biol. (2009) 1(6):a000950. https://10.1101/cshperspect.a000950
  156. Qu L, Huang S, Baltzis D, Rivas-Estilla AM, Pluquet O, Hatzoglou M, et al. Endoplasmic reticulum stress induces p53 cytoplasmic localization and prevents p53-dependent apoptosis by a pathway involving glycogen synthase kinase-3beta. Genes Dev. (2004) 18(3):261-77. https://10.1101/gad.1165804
  157. Zittermann A. vitamin D and cardiovascular disease. Anticancer Res. (2014) 34 (9):4641-8. PMID: 25202039
  158. Levita J, Wilar G, Wahyuni I, Bawono LC, Ramadaini T, Rohani R, et al. Clinical toxicology of vitamin D in pediatrics: a review and case reports. Toxics. (2023) 11(7):642. https://10.3390/toxics11070642
  159. Zittermann A, Trummer C, Theiler-Schwetz V, Pilz S. Long-term supplementation with 3200 to 4000 IU of vitamin D daily and adverse events: a systematic review and meta-analysis of randomized controlled trials. Eur J Nutr. (2023) 62(4):1833-44. https://10.1007/s00394-023-03124-w
  160. Leblond F, Poirier S, Yu C, Duquette N, Mayer G, Thorin E. The anti- hypercholesterolemic effect of low p53 expression protects vascular endothelial function in mice. PLoS One. (2014) 9(3):e92394. https://10.1371/journal.pone.0092394
  161. Tuohimaa P. vitamin D and aging. J Steroid Biochem Mol Biol. (2009) 114(1- 2):78-84. https://10.1016/j.jsbmb.2008.12.020
  162. Silverbush D, Sharan R. A systematic approach to orient the human protein­protein interaction network. Nat Commun. (2019) 10(1):3015. https://10.1038/s41467- 019-10887-6
  163. Tang H, Zeng Z, Shang C, Li Q, Liu J. Epigenetic regulation in pathology of atherosclerosis: a novel perspective. Front Genet. (2021) 12:810689. https://10.3389/ fgene.2021.810689
  164. Chen YC, Smith M, Ying YL, Makridakis M, Noonan J, Kanellakis P, et al. Quantitative proteomic landscape of unstable atherosclerosis identifies molecular signatures and therapeutic targets for plaque stabilization. Commun Biol. (2023) 6 (1):265. https://10.1038/s42003-023-04641-4
  165. Das LM, Binko AM, Traylor ZP, Peng H, Lu KQ. vitamin D improves sunburns by increasing autophagy in M2 macrophages. autophagy. (2019) 15 (5):813-26. https://10.1080/15548627.2019.1569298
  166. Lee SG, Oh J, Bong SK, Kim JS, Park S, Kim S, et al. Macrophage polarization and acceleration of atherosclerotic plaques in a swine model. PLoS One. (2018) 13(3): e0193005. https://10.1371/journal.pone.0193005
  167. Chen W, Xiao W, Liu X, Yuan P, Zhang S, Wang Y, et al. Pharmacological manipulation of macrophage autophagy effectively rejuvenates the regenerative potential of biodegrading vascular graft in aging body. Bioact Mater. (2021) 11:283-299. https://10.1016/j.bioactmat.2021.09.027
  168. Stoffels K, Overbergh L, Giulietti A, Verlinden L, Bouillon R, Mathieu C. Immune regulation of 25-hydroxyvitamin-D3-1alpha-hydroxylase in human monocytes. J Bone Miner Res. (2006) 21(1):37-47. https://10.1359/JBMR.050908
  169. Fang M, Zhong C. vitamin D receptor mediates liver ischemia and reperfusion injury by autophagy__-regulated M2 macrophage polarization. Turk J Biol. (2023) 47 (1) :120-9. https://10.55730/1300-0152.2647
  170. Jantsch J, Binger KJ, Muller DN, Titze J. macrophages in homeostatic immune function. Front Physiol. (2014) 5:146. https://10.3389/fphys.2014.00146
  171. Wu J, He S, Song Z, Chen S, Lin X, Sun H, et al. Macrophage polarization states in atherosclerosis. Front Immunol. (2023) 14:1185587. https://10.3389/fimmu.2023. 1185587
  172. Khanolkar S, Hirani S, Mishra A, Vardhan S, Hirani S, Prasad R, et al. Exploring the role of vitamin D in atherosclerosis and its impact on cardiovascular events: a comprehensive review. Cureus. (2023) 15(7):e42470. https://10.7759/cureus. 42470
  173. Bi Y, Chen J, Hu F, Liu J, Li M, Zhao L. M2 macrophages as a potential target for antiatherosclerosis treatment. Neural Plast. (2019) 2019:6724903. https://10.1155/ 2019/6724903
  174. Becker L, Nguyen L, Gill J, Kulkarni S, Pasricha PJ, Habtezion A. Age- dependent shift in macrophage polarisation causes inflammation-mediated degeneration of enteric nervous system. Gut. (2018) 67(5):827-36. https://10.1136/ gutjnl-2016-312940
  175. Behmoaras J, Gil J. Similarities and interplay between senescent cells and macrophages. J Cell Biol. (2021) 220(2):e202010162. https://10.1083/jcb.202010162
  176. Chung HY, Kim DH, Lee EK, Chung KW, Chung S, Lee B, et al. Redefining chronic inflammation in aging and age-related diseases: proposal of the senoinflammation concept. Aging Dis. (2019) 10(2):367-82. https://10.14336/AD.2018. 0324
  177. Linehan E, Fitzgerald DC. Ageing and the immune system: focus on macrophages. Eur J Microbiol Immunol (Bp). (2015) 5(1):14-24. https://10.1556/ EUJMI-D-14-00035
  178. Bobryshev YV, Ivanova EA, Chistiakov DA, Nikiforov NG, Orekhov AN. macrophages and their role in atherosclerosis: pathophysiology and transcriptome analysis. Biomed Res Int. (2016) 2016:9582430. https://10.1155/2016/958243
  179. Subramanian M, Tabas I. Dendritic cells in atherosclerosis. Semin Immunopathol. (2014) 36(1):93-102. https://10.1007/s00281-013-0400-x
  180. Moore KJ, Sheedy FJ, Fisher EA. macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol. (2013) 13(10):709-21. https://10.1038/nri3520
  181. Mosser DM, Hamidzadeh K, Goncalves R. macrophages and the maintenance of homeostasis. Cell Mol Immunol. (2021) 18(3):579-87. https://10.1038/s41423-020- 00541-3
  182. Boyle JJ. Macrophage activation in atherosclerosis: pathogenesis and pharmacology of plaque rupture. Curr Vasc Pharmacol. (2005) 3(1):63-8. https://10.2174/1570161052773861
  183. Barrett TJ. macrophages in atherosclerosis regression. Arterioscler Thromb Vasc Biol. (2020) 40(1):20-33. https://10.1161/ATVBAHA.119.312802
  184. Zhao Y, Zhang J, Zhang W, Xu Y. A myriad of roles of dendritic cells in atherosclerosis. Clin Exp Immunol. (2021) 206(1):12-27. https://10.1111/cei.13634
  185. Feig JE, Feig JL. macrophages, dendritic cells, and regression of atherosclerosis. Front Physiol. (2012) 3:286. https://10.3389/fphys.2012.00286
  186. Krzyszczyk P, Schloss R, Palmer A, Berthiaume F. The role of macrophages in acute and chronic wound healing and interventions to promote pro-wound healing phenotypes. Front Physiol. (2018) 9:419. https://10.3389/fphys.2018.00419
  187. Guo FX, Hu YW, Zheng L, Wang Q. Shear stress in autophagy and its possible mechanisms in the process of atherosclerosis. DNA Cell Biol. (2017) 36(5):335-46. https://10.1089/dna.2017.3649
  188. Seneviratne AN, Cole JE, Goddard ME, Park I, Mohri Z, Sansom S, et al. Low shear stress induces M1 macrophage polarization in murine thin-cap atherosclerotic plaques. J Mol Cell Cardiol. (2015) 89(Pt B-):168-72. https://10.1016/j.yjmcc.2015.10.034. Erratum in: J Mol Cell Cardiol. 2016;91:10.
  189. Yang F, Liu Y, Ren H, Zhou G, Yuan X, Shi X. ER-stress regulates macrophage polarization through pancreatic EIF-2alpha kinase. Cell Immunol. (2019) 336:40-7. https://10.1016/j.cellimm.2018.12.008
  190. Chipurupalli S, Samavedam U, Robinson N. Crosstalk between ER stress, autophagy and inflammation. Front Med (Lausanne). (2021) 8:758311. https://10.3389/ fmed.2021.758311
  191. Wen JH, Li DY, Liang S, Yang C, Tang JX, Liu HF. Macrophage autophagy in macrophage polarization, chronic inflammation and organ fibrosis. Front Immunol. (2022) 13:946832. https://10.3389/fimmu.2022.946832
  192. McGillis L, Bronte-Tinkew DM, Dang F, Capurro M, Prashar A, Ricciuto A, et al. vitamin D deficiency enhances expression of autophagy-regulating miR-142- 3p in mouse and “involved” IBD patient intestinal tissues. Am J Physiol Gastrointest LiverPhysiol. (2021) 321(2):G171-G184. https://10.1152/ajpgi.00398.2020
  193. Krishna SM. vitamin D as a protector of arterial health: potential role in peripheral arterial disease formation. Int J Mol Sci. (2019) 20(19):4907. https://10.3390/ijms20194907
  194. Liang S, Cai J, Li Y, Yang R. 1,25-dihydroxy-vitamin D3 induces macrophage polarization to M2 by upregulating T-cell Ig-mucin-3 expression. Mol Med Rep. (2019) 19(5):3707-13. https://10.3892/mmr.2019.10047
  195. Yin K, You Y, Swier V, Tang L, Radwan MM, Pandya AN, et al. vitamin D protects against atherosclerosis via regulation of cholesterol efflux and macrophage polarization in hypercholesterolemic swine. Arterioscler Thromb Vasc Biol. (2015) 35(11):2432-42. https://10.1161/ATVBAHA.115.306132
  196. Szeto FL, Reardon CA, Yoon D, Wang Y, Wong KE, Chen Y, et al. vitamin D receptor signaling inhibits atherosclerosis in mice. Mol Endocrinol. (2012) 26 (7):1091—101. https://10.1210/me.2011-1329
  197. Singh S, Torzewski M. Fibroblasts and their pathological functions in the fibrosis of aortic valve sclerosis and atherosclerosis. Biomolecules. (2019) 9(9):472. https://10.3390/biom9090472
  198. Ahn J, Peters U, Albanes D, Purdue MP, Abnet CC, Chatterjee N, et al. Serum vitamin D concentration and prostate cancer risk: a nested case-control study. J Natl Cancer Inst. (2008) 100(11):796-804.
  199. Yuk JM, Shin DM, Lee HM, Yang CS, Jin HS, Kim KK, et al. vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin. Cell Host Microbe. (2009) 6(3):231-43. https://10.1016/j.chom.2009.08.004
  200. Nguyen LK, Kholodenko BN, von Kriegsheim A. Rac1 and RhoA: networks, loops and bistability. Small GTPases. (2018) 9(4):316-21. https://10.1080/21541248. 2016.1224399
  201. Quiroga X, Walani N, Disanza A, Chavero A, Mittens A, Tebar F, et al. A mechanosensing mechanism controls plasma membrane shape homeostasis at the nanoscale. Elife. (2023) 12:e72316. https://10.7554/eLife.72316
  202. Khundmiri SJ, Murray RD, Lederer E. PTH and vitamin D. Compr Physiol. (2016) 6(2):561-601. https://10.1002/cphy.c140071
  203. Robens JM, Yeow-Fong L, Ng E, Hall C, Manser E. Regulation of IRSp53- dependent filopodial dynamics by antagonism between 14 and 3-3 binding and SH3-mediated localization. Mol Cell Biol. (2010) 30(3):829-44. https://10.1128/MCB. 01574-08
  204. Bisi S, Marchesi S, Rizvi A, Carra D, Beznoussenko GV, Ferrara I, et al. IRSp53 controls plasma membrane shape and polarized transport at the nascent lumen in epithelial tubules. Nat Commun. (2020) 11(1):3516. https://10.1038/s41467-020-17091-x
  205. Zhang HH, Wang W, Feng L, Yang Y, Zheng J, Huang L, et al. S-nitrosylation of Cofilin-1 serves as a novel pathway for VEGF-stimulated endothelial cell migration. J Cell Physiol. (2015) 230(2):406-17. https://10.1002/jcp.24724
  206. Acevedo A, Gonzalez-Billault C. Crosstalk between Rac1-mediated actin regulation and ROS production. Free Radic Biol Med. (2018) 116:101-13. https://10.1016/j.freeradbiomed.2018.01.008
  207. Lâhnemann D, Koster J, Szczurek E, McCarthy DJ, Hicks SC, Robinson MD, et al. Eleven grand challenges in single-cell data science. Genome Biol. (2020) 21 (1):31. https://10.1186/s13059-020-1926-6
  208. Kustatscher G, Hodl M, Rullmann E, Grabowski P, Fiagbedzi E, Groth A, et al. Higher-order modular regulation of the human proteome. Mol Syst Biol. (2023) 19(5): e9503. https://10.15252/msb.20209503
  209. Singh MS, Pasumarthy R, Vaidya U, Leonhardt S. On quantification and maximization of information transfer in network dynamical systems. Sci Rep. (2023) 13(1):5588. https://10.1038/s41598-023-32762-7
  210. e la Guia-Galipienso F, Martinez-Ferran M, Vallecillo N, Lavie CJ, Sanchis- Gomar F, Pareja-Galeano H. vitamin D and cardiovascular health. Clin Nutr. (2021) 40(5):2946-57. https://10.1016/j.clnu.2020.12.025
  211. Molinari C, Morsanuto V, Polli S, Uberti F. Cooperative effects of Q10, vitamin D3, and L-arginine on cardiac and endothelial cells. J Vasc Res. (2018) 55(1):47-60. https://10.1159/000484928
  212. Tewani GR, Silwal K, Sharma G, Yadav D, Siddiqui A, Kriplani S, et al. Effect of medically supervised prolonged fasting therapy on vitamin D, B12, body weight, body mass index, vitality and quality of life: a randomized control trial. Nutr Metab Insights. (2022) 15:11786388221130560. https://10.1177/11786388221130560

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21414 D, CVD, macrophage polarization_CompressPdf.pdf admin 10 Jul, 2024 594.14 Kb 29