Proarrhythmic Remodeling of Calcium Homeostasis in Cardiac Disease; Implications for Diabetes and Obesity

Overview

Journal Front Physiol

Date 2018 Nov 15

PMID 30425651

Citations 22

Authors

Shanna Hamilton

Dmitry Terentyev

Affiliations

Soon will be listed here.

Abstract

A rapid growth in the incidence of diabetes and obesity has transpired to a major heath issue and economic burden in the postindustrial world, with more than 29 million patients affected in the United States alone. Cardiovascular defects have been established as the leading cause of mortality and morbidity of diabetic patients. Over the last decade, significant progress has been made in delineating mechanisms responsible for the diminished cardiac contractile function and enhanced propensity for malignant cardiac arrhythmias characteristic of diabetic disease. Rhythmic cardiac contractility relies upon the precise interplay between several cellular Ca transport protein complexes including plasmalemmal L-type Ca channels (LTCC), Na-Ca exchanger (NCX1), Sarco/endoplasmic Reticulum (SR) Ca-ATPase (SERCa2a) and ryanodine receptors (RyR2s), the SR Ca release channels. Here we provide an overview of changes in Ca homeostasis in diabetic ventricular myocytes and discuss the therapeutic potential of targeting Ca handling proteins in the prevention of diabetes-associated cardiomyopathy and arrhythmogenesis.

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References

Wehrens X, Lehnart S, Reiken S, Vest J, Wronska A, Marks A . Ryanodine receptor/calcium release channel PKA phosphorylation: a critical mediator of heart failure progression. Proc Natl Acad Sci U S A. 2006; 103(3):511-8. PMC: 1334677. DOI: 10.1073/pnas.0510113103. View

Belke D, Swanson E, Dillmann W . Decreased sarcoplasmic reticulum activity and contractility in diabetic db/db mouse heart. Diabetes. 2004; 53(12):3201-8. DOI: 10.2337/diabetes.53.12.3201. View

Marx S, Reiken S, Hisamatsu Y, Jayaraman T, Burkhoff D, Rosemblit N . PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts. Cell. 2000; 101(4):365-76. DOI: 10.1016/s0092-8674(00)80847-8. View

Kaneko N, Matsuda R, Toda M, Shimamoto K . Inhibition of annexin V-dependent Ca2+ movement in large unilamellar vesicles by K201, a new 1,4-benzothiazepine derivative. Biochim Biophys Acta. 1997; 1330(1):1-7. DOI: 10.1016/s0005-2736(97)00132-6. View

Lahat H, Pras E, Olender T, Avidan N, Ben-Asher E, Man O . A missense mutation in a highly conserved region of CASQ2 is associated with autosomal recessive catecholamine-induced polymorphic ventricular tachycardia in Bedouin families from Israel. Am J Hum Genet. 2001; 69(6):1378-84. PMC: 1235548. DOI: 10.1086/324565. View

Mochizuki M, Yano M, Oda T, Tateishi H, Kobayashi S, Yamamoto T . Scavenging free radicals by low-dose carvedilol prevents redox-dependent Ca2+ leak via stabilization of ryanodine receptor in heart failure. J Am Coll Cardiol. 2007; 49(16):1722-32. DOI: 10.1016/j.jacc.2007.01.064. View

Zima A, Blatter L . Redox regulation of cardiac calcium channels and transporters. Cardiovasc Res. 2006; 71(2):310-21. DOI: 10.1016/j.cardiores.2006.02.019. View

Okatan E, Durak A, Turan B . Electrophysiological basis of metabolic-syndrome-induced cardiac dysfunction. Can J Physiol Pharmacol. 2016; 94(10):1064-1073. DOI: 10.1139/cjpp-2015-0531. View

Greenberg B, Butler J, Felker G, Ponikowski P, Voors A, Desai A . Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2): a randomised, multinational, double-blind, placebo-controlled, phase 2b trial. Lancet. 2016; 387(10024):1178-86. DOI: 10.1016/S0140-6736(16)00082-9. View

10.

Venetucci L, Denegri M, Napolitano C, Priori S . Inherited calcium channelopathies in the pathophysiology of arrhythmias. Nat Rev Cardiol. 2012; 9(10):561-75. DOI: 10.1038/nrcardio.2012.93. View

11.

Monte F, Harding S, Dec G, Gwathmey J, Hajjar R . Targeting phospholamban by gene transfer in human heart failure. Circulation. 2002; 105(8):904-7. PMC: 1249505. DOI: 10.1161/hc0802.105564. View

12.

Ather S, Wang W, Wang Q, Li N, Anderson M, Wehrens X . Inhibition of CaMKII phosphorylation of RyR2 prevents inducible ventricular arrhythmias in mice with Duchenne muscular dystrophy. Heart Rhythm. 2012; 10(4):592-9. PMC: 3605194. DOI: 10.1016/j.hrthm.2012.12.016. View

13.

Liu B, Walton S, Ho H, Belevych A, Tikunova S, Bonilla I . Gene Transfer of Engineered Calmodulin Alleviates Ventricular Arrhythmias in a Calsequestrin-Associated Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia. J Am Heart Assoc. 2018; 7(10). PMC: 6015318. DOI: 10.1161/JAHA.117.008155. View

14.

Faggioni M, Kryshtal D, Knollmann B . Calsequestrin mutations and catecholaminergic polymorphic ventricular tachycardia. Pediatr Cardiol. 2012; 33(6):959-67. PMC: 3393815. DOI: 10.1007/s00246-012-0256-1. View

15.

Belevych A, Terentyev D, Terentyeva R, Ho H, Gyorke I, Bonilla I . Shortened Ca2+ signaling refractoriness underlies cellular arrhythmogenesis in a postinfarction model of sudden cardiac death. Circ Res. 2012; 110(4):569-77. PMC: 4068617. DOI: 10.1161/CIRCRESAHA.111.260455. View

16.

Laakso M . Diabetes as a 'cardiovascular disease equivalent': implications for treatment. Nat Clin Pract Cardiovasc Med. 2008; 5(11):682-3. DOI: 10.1038/ncpcardio1344. View

17.

Mathews C, Langley S, Leiter E . New mouse model to study islet transplantation in insulin-dependent diabetes mellitus. Transplantation. 2002; 73(8):1333-6. DOI: 10.1097/00007890-200204270-00024. View

18.

Knollmann B, Chopra N, Hlaing T, Akin B, Yang T, Ettensohn K . Casq2 deletion causes sarcoplasmic reticulum volume increase, premature Ca2+ release, and catecholaminergic polymorphic ventricular tachycardia. J Clin Invest. 2006; 116(9):2510-20. PMC: 1551934. DOI: 10.1172/JCI29128. View

19.

Tian C, Shao C, Moore C, Kutty S, Walseth T, Desouza C . Gain of function of cardiac ryanodine receptor in a rat model of type 1 diabetes. Cardiovasc Res. 2011; 91(2):300-9. PMC: 3125072. DOI: 10.1093/cvr/cvr076. View

20.

Shao C, Wehrens X, Wyatt T, Parbhu S, Rozanski G, Patel K . Exercise training during diabetes attenuates cardiac ryanodine receptor dysregulation. J Appl Physiol (1985). 2009; 106(4):1280-92. PMC: 2698642. DOI: 10.1152/japplphysiol.91280.2008. View