Remodeling of T-system and Proteins Underlying Excitation-contraction Coupling in Aging Versus Failing Human Heart

Overview

Journal NPJ Aging Mech Dis

Specialty Geriatrics

Date 2021 May 29

PMID 34050186

Citations 9

Authors

Yankun Lyu

Vipin K Verma

Younjee Lee

Iosif Taleb

Rachit Badolia

Thirupura S Shankar

Christos P Kyriakopoulos

Craig H Selzman

William Caine

Rami Alharethi

Sutip Navankasattusas

Thomas Seidel

Stavros G Drakos

Frank B Sachse

Affiliations

Soon will be listed here.

Abstract

It is well established that the aging heart progressively remodels towards a senescent phenotype, but alterations of cellular microstructure and their differences to chronic heart failure (HF) associated remodeling remain ill-defined. Here, we show that the transverse tubular system (t-system) and proteins underlying excitation-contraction coupling in cardiomyocytes are characteristically remodeled with age. We shed light on mechanisms of this remodeling and identified similarities and differences to chronic HF. Using left ventricular myocardium from donors and HF patients with ages between 19 and 75 years, we established a library of 3D reconstructions of the t-system as well as ryanodine receptor (RyR) and junctophilin 2 (JPH2) clusters. Aging was characterized by t-system alterations and sarcolemmal dissociation of RyR clusters. This remodeling was less pronounced than in HF and accompanied by major alterations of JPH2 arrangement. Our study indicates that targeting sarcolemmal association of JPH2 might ameliorate age-associated deficiencies of heart function.

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