Cellular Senescence Affects Cardiac Regeneration and Repair in Ischemic Heart Disease

Overview

Journal Aging Dis

Specialty Geriatrics

Date 2021 Apr 5

PMID 33815882

Citations 21

Authors

Chi Yan

Zhimeng Xu

Weiqiang Huang

Affiliations

Soon will be listed here.

Abstract

Ischemic heart disease (IHD) is defined as a syndrome of ischemic cardiomyopathy. Myogenesis and angiogenesis in the ischemic myocardium are important for cardiomyocyte (CM) survival, improving cardiac function and decreasing the progression of heart failure after IHD. Cellular senescence is a state of permanent irreversible cell cycle arrest caused by stress that results in a decline in cellular functions, such as proliferation, migration, homing, and differentiation. In addition, senescent cells produce the senescence-associated secretory phenotype (SASP), which affects the tissue microenvironment and surrounding cells by secreting proinflammatory cytokines, chemokines, growth factors, and extracellular matrix degradation proteins. The accumulation of cardiovascular-related senescent cells, including vascular endothelial cells (VECs), vascular smooth muscle cells (VSMCs), CMs and progenitor cells, is an important risk factor of cardiovascular diseases, such as vascular aging, atherosclerotic plaque formation, myocardial infarction (MI) and ventricular remodeling. This review summarizes the processes of angiogenesis, myogenesis and cellular senescence after IHD. In addition, this review focuses on the relationship between cellular senescence and cardiovascular disease and the mechanism of cellular senescence. Finally, we discuss a potential therapeutic strategy for MI targeting senescent cells.

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References

Kobayashi K, Maeda K, Takefuji M, Kikuchi R, Morishita Y, Hirashima M . Dynamics of angiogenesis in ischemic areas of the infarcted heart. Sci Rep. 2017; 7(1):7156. PMC: 5540926. DOI: 10.1038/s41598-017-07524-x. View

Zhao G, Wang H, Xu C, Wang P, Chen J, Wang P . SIRT6 delays cellular senescence by promoting p27Kip1 ubiquitin-proteasome degradation. Aging (Albany NY). 2016; 8(10):2308-2323. PMC: 5115890. DOI: 10.18632/aging.101038. View

Ebeid D, Khalafalla F, Broughton K, Monsanto M, Esquer C, Sacchi V . Pim1 maintains telomere length in mouse cardiomyocytes by inhibiting TGFβ signalling. Cardiovasc Res. 2020; 117(1):201-211. PMC: 7797214. DOI: 10.1093/cvr/cvaa066. View

Saheera S, Potnuri A, Nair R . Modulation of cardiac stem cell characteristics by metoprolol in hypertensive heart disease. Hypertens Res. 2018; 41(4):253-262. DOI: 10.1038/s41440-018-0015-7. View

. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018; 392(10159):1736-1788. PMC: 6227606. DOI: 10.1016/S0140-6736(18)32203-7. View

Kang C . Senolytics and Senostatics: A Two-Pronged Approach to Target Cellular Senescence for Delaying Aging and Age-Related Diseases. Mol Cells. 2019; 42(12):821-827. PMC: 6939651. DOI: 10.14348/molcells.2019.0298. View

En A, Takauji Y, Ayusawa D, Fujii M . The role of lamin B receptor in the regulation of senescence-associated secretory phenotype (SASP). Exp Cell Res. 2020; 390(1):111927. DOI: 10.1016/j.yexcr.2020.111927. View

Palmer A, Gustafson B, Kirkland J, Smith U . Cellular senescence: at the nexus between ageing and diabetes. Diabetologia. 2019; 62(10):1835-1841. PMC: 6731336. DOI: 10.1007/s00125-019-4934-x. View

Vicinanza C, Aquila I, Scalise M, Cristiano F, Marino F, Cianflone E . Adult cardiac stem cells are multipotent and robustly myogenic: c-kit expression is necessary but not sufficient for their identification. Cell Death Differ. 2017; 24(12):2101-2116. PMC: 5686347. DOI: 10.1038/cdd.2017.130. View

10.

Chi C, Li D, Jiang Y, Tong J, Fu H, Wu Y . Vascular smooth muscle cell senescence and age-related diseases: State of the art. Biochim Biophys Acta Mol Basis Dis. 2019; 1865(7):1810-1821. DOI: 10.1016/j.bbadis.2018.08.015. View

11.

Laberge R, Sun Y, Orjalo A, Patil C, Freund A, Zhou L . MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nat Cell Biol. 2015; 17(8):1049-61. PMC: 4691706. DOI: 10.1038/ncb3195. View

12.

Panda A, Grammatikakis I, Kim K, De S, Martindale J, Munk R . Identification of senescence-associated circular RNAs (SAC-RNAs) reveals senescence suppressor CircPVT1. Nucleic Acids Res. 2016; 45(7):4021-4035. PMC: 5397146. DOI: 10.1093/nar/gkw1201. View

13.

Zhang X, Wang Y, Zhao R, Hu X, Zhang B, Lv X . Folic Acid Supplementation Suppresses Sleep Deprivation-Induced Telomere Dysfunction and Senescence-Associated Secretory Phenotype (SASP). Oxid Med Cell Longev. 2020; 2019:4569614. PMC: 6948340. DOI: 10.1155/2019/4569614. View

14.

He S, Sharpless N . Senescence in Health and Disease. Cell. 2017; 169(6):1000-1011. PMC: 5643029. DOI: 10.1016/j.cell.2017.05.015. View

15.

Zhang L, Bhaloo S, Chen T, Zhou B, Xu Q . Role of Resident Stem Cells in Vessel Formation and Arteriosclerosis. Circ Res. 2018; 122(11):1608-1624. PMC: 5976231. DOI: 10.1161/CIRCRESAHA.118.313058. View

16.

Chen C, Chen T, Li Y, Xu Y . miR-19a/19b improves the therapeutic potential of mesenchymal stem cells in a mouse model of myocardial infarction. Gene Ther. 2020; 28(1-2):29-37. DOI: 10.1038/s41434-020-0122-3. View

17.

Yang D, Yang K, Yang M . Circular RNA in Aging and Age-Related Diseases. Adv Exp Med Biol. 2018; 1086:17-35. DOI: 10.1007/978-981-13-1117-8_2. View

18.

Xu C, Sang B, Liu G, Li J, Zhang X, Liu L . SENEBLOC, a long non-coding RNA suppresses senescence via p53-dependent and independent mechanisms. Nucleic Acids Res. 2020; 48(6):3089-3102. PMC: 7102969. DOI: 10.1093/nar/gkaa063. View

19.

Kang C, Xu Q, Martin T, Li M, Demaria M, Aron L . The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. Science. 2015; 349(6255):aaa5612. PMC: 4942138. DOI: 10.1126/science.aaa5612. View

20.

Marchionni S, Sell C, Lorenzini A . Development and Longevity: Cellular and Molecular Determinants - A Mini-Review. Gerontology. 2020; 66(3):223-230. DOI: 10.1159/000505327. View