Self-eating and Heart: The Emerging Roles of Autophagy in Calcific Aortic Valve Disease

Overview

Journal Aging Dis

Specialty Geriatrics

Date 2021 Aug 3

PMID 34341709

Citations 5

Authors

Yunlong Fan

Jiakang Shao

Shixiong Wei

Chao Song

Yanan Li

Shengli Jiang

Affiliations

Soon will be listed here.

Abstract

Autophagy is a self-degradative pathway by which subcellular elements are broken down intracellularly to maintain cellular homeostasis. Cardiac autophagy commonly decreases with aging and is accompanied by the accumulation of misfolded proteins and dysfunctional organelles, which are undesirable to the cell. Reduction of autophagy over time leads to aging-related cardiac dysfunction and is inversely related to longevity. However, despite the increasing interest in autophagy in cardiac diseases and aging, the process remains an undervalued and disregarded object in calcific valvular disease. Neither the nature through which autophagy is triggered nor the interplay between autophagic machinery and targeted molecules during aortic valve calcification are fully understood. Recently, the upregulation of autophagy has been shown to result in cardioprotective effects against cell death as well as its origin. Here, we review the evidence that shows how autophagy can be both beneficial and detrimental as it pertains to aortic valve calcification in the heart.

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References

Zhou X, Chen J . Is treatment with trimetazidine beneficial in patients with chronic heart failure?. PLoS One. 2014; 9(5):e94660. PMC: 4010408. DOI: 10.1371/journal.pone.0094660. View

Lindman B, Clavel M, Mathieu P, Iung B, Lancellotti P, Otto C . Calcific aortic stenosis. Nat Rev Dis Primers. 2016; 2():16006. PMC: 5127286. DOI: 10.1038/nrdp.2016.6. View

Enomoto H, Mittal N, Inomata T, Arimura T, Izumi T, Kimura A . Dilated cardiomyopathy-linked heat shock protein family D member 1 mutations cause up-regulation of reactive oxygen species and autophagy through mitochondrial dysfunction. Cardiovasc Res. 2020; 117(4):1118-1131. DOI: 10.1093/cvr/cvaa158. View

Buskohl P, Sun M, Sun M, Thompson R, Butcher J . Serotonin potentiates transforming growth factor-beta3 induced biomechanical remodeling in avian embryonic atrioventricular valves. PLoS One. 2012; 7(8):e42527. PMC: 3412853. DOI: 10.1371/journal.pone.0042527. View

Taneike M, Yamaguchi O, Nakai A, Hikoso S, Takeda T, Mizote I . Inhibition of autophagy in the heart induces age-related cardiomyopathy. Autophagy. 2010; 6(5):600-6. DOI: 10.4161/auto.6.5.11947. View

Nakai A, Yamaguchi O, Takeda T, Higuchi Y, Hikoso S, Taniike M . The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nat Med. 2007; 13(5):619-24. DOI: 10.1038/nm1574. View

Rothermel B, Hill J . Autophagy in load-induced heart disease. Circ Res. 2008; 103(12):1363-9. PMC: 2607044. DOI: 10.1161/CIRCRESAHA.108.186551. View

Yin Yip C, Chen J, Zhao R, Simmons C . Calcification by valve interstitial cells is regulated by the stiffness of the extracellular matrix. Arterioscler Thromb Vasc Biol. 2009; 29(6):936-42. DOI: 10.1161/ATVBAHA.108.182394. View

Song R, Fullerton D, Ao L, Zhao K, Meng X . An epigenetic regulatory loop controls pro-osteogenic activation by TGF-β1 or bone morphogenetic protein 2 in human aortic valve interstitial cells. J Biol Chem. 2017; 292(21):8657-8666. PMC: 5448094. DOI: 10.1074/jbc.M117.783308. View

10.

Shi B, Ma M, Zheng Y, Pan Y, Lin X . mTOR and Beclin1: Two key autophagy-related molecules and their roles in myocardial ischemia/reperfusion injury. J Cell Physiol. 2019; 234(8):12562-12568. DOI: 10.1002/jcp.28125. View

11.

Kloxin A, Benton J, Anseth K . In situ elasticity modulation with dynamic substrates to direct cell phenotype. Biomaterials. 2009; 31(1):1-8. PMC: 2791128. DOI: 10.1016/j.biomaterials.2009.09.025. View

12.

Cao K, Sucosky P . Computational comparison of regional stress and deformation characteristics in tricuspid and bicuspid aortic valve leaflets. Int J Numer Method Biomed Eng. 2016; 33(3). DOI: 10.1002/cnm.2798. View

13.

Dvornikov A, Wang M, Yang J, Zhu P, Le T, Lin X . Phenotyping an adult zebrafish lamp2 cardiomyopathy model identifies mTOR inhibition as a candidate therapy. J Mol Cell Cardiol. 2019; 133:199-208. PMC: 6705397. DOI: 10.1016/j.yjmcc.2019.06.013. View

14.

Sciarretta S, Maejima Y, Zablocki D, Sadoshima J . The Role of Autophagy in the Heart. Annu Rev Physiol. 2017; 80:1-26. DOI: 10.1146/annurev-physiol-021317-121427. View

15.

Fu Z, Luo B, Li M, Peng B, Wang Z . Effects of Raloxifene on the Proliferation and Apoptosis of Human Aortic Valve Interstitial Cells. Biomed Res Int. 2016; 2016:5473204. PMC: 5141314. DOI: 10.1155/2016/5473204. View

16.

Chen K, Kobayashi S, Xu X, Viollet B, Liang Q . AMP activated protein kinase is indispensable for myocardial adaptation to caloric restriction in mice. PLoS One. 2013; 8(3):e59682. PMC: 3602170. DOI: 10.1371/journal.pone.0059682. View

17.

Sikura K, Potor L, Szerafin T, Oros M, Nagy P, Mehes G . Hydrogen sulfide inhibits calcification of heart valves; implications for calcific aortic valve disease. Br J Pharmacol. 2019; 177(4):793-809. PMC: 7024713. DOI: 10.1111/bph.14691. View

18.

He C, Zhu H, Zhang W, Okon I, Wang Q, Li H . 7-Ketocholesterol induces autophagy in vascular smooth muscle cells through Nox4 and Atg4B. Am J Pathol. 2013; 183(2):626-37. PMC: 3730774. DOI: 10.1016/j.ajpath.2013.04.028. View

19.

Zhu H, Zhang Y . Life and Death Partners in Post-PCI Restenosis: Apoptosis, Autophagy, and The Cross-talk Between Them. Curr Drug Targets. 2016; 19(9):1003-1008. DOI: 10.2174/1389450117666160625072521. View

20.

Somers P, Knaapen M, Kockx M, Van Cauwelaert P, Bortier H, Mistiaen W . Histological evaluation of autophagic cell death in calcified aortic valve stenosis. J Heart Valve Dis. 2006; 15(1):43-7. View