SIRT1 Activation Attenuates the Cardiac Dysfunction Induced by Endothelial Cell-Specific Deletion of CRIF1

Piao, Shuyu and Lee, Ikjun and Jin, Seon-Ah and Kim, Seonhee and Nagar, Harsha and Choi, Su-jeong and Jeon, Byeong Hwa and Kim, Cuk-Seong (2021) SIRT1 Activation Attenuates the Cardiac Dysfunction Induced by Endothelial Cell-Specific Deletion of CRIF1. Biomedicines, 9 (1). p. 52. ISSN 2227-9059

[thumbnail of biomedicines-09-00052-v2.pdf] Text
biomedicines-09-00052-v2.pdf - Published Version

Download (12MB)

Abstract

The CR6-interacting factor1 (CRIF1) mitochondrial protein is indispensable for peptide synthesis and oxidative phosphorylation. Cardiomyocyte-specific deletion of CRIF1 showed impaired mitochondrial function and cardiomyopathy. We developed an endothelial cell-specific CRIF1 deletion mouse to ascertain whether dysfunctional endothelial CRIF1 influences cardiac function and is mediated by the antioxidant protein sirtuin 1 (SIRT1). We also examined the effect of the potent SIRT1 activator SRT1720 on cardiac dysfunction. Mice with endothelial cell-specific CRIF1 deletion showed an increased heart-to-body weight ratio, increased lethality, and markedly reduced fractional shortening of the left ventricle, resulting in severe cardiac dysfunction. Moreover, endothelial cell-specific CRIF1 deletion resulted in mitochondrial dysfunction, reduced ATP levels, inflammation, and excessive oxidative stress in heart tissues, associated with decreased SIRT1 expression. Intraperitoneal injection of SRT1720 ameliorated cardiac dysfunction by activating endothelial nitric oxide synthase, reducing oxidative stress, and inhibiting inflammation. Furthermore, the decreased endothelial junction-associated protein zonula occludens-1 in CRIF1-deleted mice was significantly recovered after SRT1720 treatment. Our results suggest that endothelial CRIF1 plays an important role in maintaining cardiac function, and that SIRT1 induction could be a therapeutic strategy for endothelial dysfunction-induced cardiac dysfunction.

Item Type: Article
Subjects: European Scholar > Chemical Science
Depositing User: Managing Editor
Date Deposited: 20 Dec 2022 11:53
Last Modified: 26 Dec 2023 04:40
URI: http://article.publish4promo.com/id/eprint/312

Actions (login required)

View Item
View Item