Genetic risk factors for vascular aging: molecular mechanisms, polymorphism of candidate genes and gene networks
https://doi.org/10.15829/1560-4071-2019-10-78-85
Abstract
Age is considered an independent and primary risk factor in the development of cardiovascular disease. Aging of vascular cells induces complex changes in the structure and functions of the vasculature. The article discusses a number of molecular genetic mechanisms involved in the pathogenesis of vascular aging: cell and mitochondrial dysfunction, endothelial dysfunction, depletion of the progenitor cell pool, shortening and damage to telomeres, chronic inflammation, oxidative stress, and dysregulation of vascular tone. There is more and more evidence of cross-involvement in the vascular aging processes of candidate genes (such as ACE, SIRT1, TERC, FOXO1, FOXO3, APOE, NOS3) associated with life expectancy and cardiovascular diseases. For 26 genes involved in the presented molecular mechanisms of vascular aging, sites of functional polymorphisms are given. Understanding the main pathophysiological changes caused by vascular aging makes it possible to choose a preventive strategy. Modern approaches for better predicting of genetic risk are discussed in conclusion using the example of visualization of vascular aging genes network.
Keywords
vascular aging,
endothelial dysfunction,
arterial stiffness,
oxidative stress,
genetic risk,
gene network
Supporting agencies: The study was financially supported by the RFBR in the framework of scientific project № 19 315-80032
About the Authors
A. A. Slepukhina
Institute of Chemical Biology and Fundamental Medicine
Russian Federation
Competing Interests: not
Russian Federation
Novosibirsk
Competing Interests: not
E. M. Zelenskaya
Institute of Chemical Biology and Fundamental Medicine
Russian Federation
Competing Interests: not
Russian Federation
Novosibirsk
Competing Interests: not
G. I. Lifshits
Institute of Chemical Biology and Fundamental Medicine; Novosibirsk State Medical University
Competing Interests: not
Novosibirsk
Competing Interests: not
References
1. Vishram JKK. Prognostic interactions between cardiovascular risk factors. Dan Med J. 2014;61(7):B4892. http://www.ncbi.nlm.nih.gov/pubmed/25123126. Accessed June 21, 2019.
2. Jia G, Aroor AR, DeMarco VG, Martinez-Lemus LA, Meininger GA, Sowers JR. Vascular stiffness in insulin resistance and obesity. Front Physiol. 2015;6:231. doi:10.3389/fphys.2015.00231
3. Niiranen TJ, Kalesan B, Larson MG, et al. Aortic–Brachial Arterial Stiffness Gradient and Cardiovascular Risk in the Community. Hypertension. 2017;69(6):1022-1028. doi:10.1161/HYPERTENSIONAHA.116.08917
4. Hohensinner PJ, Kaun C, Buchberger E, et al. Age intrinsic loss of telomere protection via TRF1 reduction in endothelial cells. Biochim Biophys Acta - Mol Cell Res. 2016;1863(2):360-367. doi:10.1016/J.BBAMCR.2015.11.034
5. Rossman MJ, Kaplon RE, Hill SD, et al. Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function. Am J Physiol Circ Physiol. 2017;313(5):H890-H895. doi:10.1152/ajpheart.00416.2017
6. Uryga AK, Bennett MR. Ageing induced vascular smooth muscle cell senescence in atherosclerosis. J Physiol. 2016;594(8):2115-2124. doi:10.1113/JP270923
7. Jia G, Aroor AR, DeMarco VG, Martinez-Lemus LA, Meininger GA, Sowers JR. Vascular stiffness in insulin resistance and obesity. Front Physiol. 2015;6:231. doi:10.3389/fphys.2015.00231
8. Donato AJ, Morgan RG, Walker AE, Lesniewski LA. Cellular and molecular biology of aging endothelial cells. J Mol Cell Cardiol. 2015;89(Pt B):122-135. doi:10.1016/j.yjmcc.2015.01.021
9. Ungvari Z, Tarantini S, Donato AJ, Galvan V, Csiszar A. Mechanisms of Vascular Aging. Circ Res. 2018;123(7):849-867. doi:10.1161/CIRCRESAHA.118.311378
10. Khan SY, Awad EM, Oszwald A, et al. Premature senescence of endothelial cells upon chronic exposure to TNFα can be prevented by N-acetyl cysteine and plumericin. Sci Rep. 2017;7:39501. doi:10.1038/srep39501
11. Katsuumi G, Shimizu I, Yoshida Y, Minamino T. Vascular Senescence in Cardiovascular and Metabolic Diseases. Front Cardiovasc Med. 2018;5:18. doi:10.3389/fcvm.2018.00018
12. Yeh J-K, Wang C-Y. Telomeres and Telomerase in Cardiovascular Diseases. Genes (Basel). 2016;7(9). doi:10.3390/genes7090058
13. Zgheib NK, Sleiman F, Nasreddine L, et al. Short Telomere Length is Associated with Aging, Central Obesity, Poor Sleep and Hypertension in Lebanese Individuals. Aging Dis. 2018;9(1):77-89. doi:10.14336/AD.2017.0310
14. Kitada M, Ogura Y, Koya D. The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis. Aging (Albany NY). 2016;8(10):2290-2307. doi:10.18632/aging.101068
15. Zarzuelo MJ, López-Sepúlveda R, Sánchez M, et al. SIRT1 inhibits NADPH oxidase activation and protects endothelial function in the rat aorta: implications for vascular aging. Biochem Pharmacol. 2013;85(9):1288-1296. doi:10.1016/j.bcp.2013.02.015
16. Wang Y-Q, Cao Q, Wang F, et al. SIRT1 Protects Against Oxidative Stress-Induced Endothelial Progenitor Cells Apoptosis by Inhibiting FOXO3a via FOXO3a Ubiquitination and Degradation. J Cell Physiol. 2015;230(9):2098-2107. doi:10.1002/jcp.24938
17. Abbas M, Jesel L, Auger C, et al. Endothelial Microparticles From Acute Coronary Syndrome Patients Induce Premature Coronary Artery Endothelial Cell Aging and Thrombogenicity. Circulation. 2017;135(3):280-296. doi:10.1161/CIRCULATIONAHA.116.017513
18. Mikael L de R, Paiva AMG de, Gomes MM, et al. Vascular Aging and Arterial Stiffness. Arq Bras Cardiol. 2017. doi:10.5935/abc.20170091
19. Park S, Lee J-Y, Kim B-K, et al. Lack of association between arterial stiffness and genetic variants by genome-wide association scan. Blood Press. 2015;24(4):258-261. doi:10.3109/08037051.2015.1049430
20. Mitchell GF, Verwoert GC, Tarasov K V, et al. Common genetic variation in the 3’-BCL11B gene desert is associated with carotid-femoral pulse wave velocity and excess cardiovascular disease risk: the AortaGen Consortium. Circ Cardiovasc Genet. 2012;5(1):81-90. doi:10.1161/CIRCGENETICS.111.959817
21. Warde-Farley D, Donaldson SL, Comes O, et al. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 2010;38(suppl_2):W214-W220. doi:10.1093/nar/gkq537
22. Natarajan P, Young R, Stitziel NO, et al. Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention SettingClinical Perspective. Circulation. 2017;135(22):2091-2101. doi:10.1161/CIRCULATIONAHA.116.024436
23. Galmés S, Cifre M, Palou A, Oliver P, Serra F. A Genetic Score of Predisposition to Low-Grade Inflammation Associated with Obesity May Contribute to Discern Population at Risk for Metabolic Syndrome. Nutrients. 2019;11(2). doi:10.3390/nu11020298
24. Pereira A, Mendonça MI, Borges S, et al. Genetic Risk Analysis of Coronary Artery Disease in a Population-based Study in Portugal, Using a Genetic Risk Score of 31 Variants. Arq Bras Cardiol. 2018;111(1):50-61. doi:10.5935/abc.20180107
25. Oguz C, Sen SK, Davis AR, Fu Y-P, O’Donnell CJ, Gibbons GH. Genotype-driven identification of a molecular network predictive of advanced coronary calcium in ClinSeq® and Framingham Heart Study cohorts. BMC Syst Biol. 2017;11(1):99. doi:10.1186/s12918-017-0474-5
Review
For citations:
Slepukhina A.A., Zelenskaya E.M., Lifshits G.I. Genetic risk factors for vascular aging: molecular mechanisms, polymorphism of candidate genes and gene networks. Russian Journal of Cardiology. 2019;(10):78-85. (In Russ.) https://doi.org/10.15829/1560-4071-2019-10-78-85
Views:
1172
Email this article 