Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart
Lyu Y, Verma VK, Lee Y, Taleb I, Badolia R, Shankar TS, Kyriakopoulos CP, Selzman CH, Caine W, Alharethi R, Navankasattusas S, Seidel T, Drakos SG, Sachse FB (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 7
Journal Issue: 1
DOI: 10.1038/s41514-021-00066-7
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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APA:
Lyu, Y., Verma, V.K., Lee, Y., Taleb, I., Badolia, R., Shankar, T.S.,... Sachse, F.B. (2021). Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart. npj Aging and Mechanisms of Disease, 7(1). https://doi.org/10.1038/s41514-021-00066-7
MLA:
Lyu, Yankun, et al. "Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart." npj Aging and Mechanisms of Disease 7.1 (2021).
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