Cardiomyocyte-Specific Deletion of Sirtuin 5 Accelerates the Development of Heart Failure Upon Dysregulating Purine Metabolism.

ABSTRACT:

Aim

Sirtuin 5 (SIRT5), a mitochondrial NAD⁺-dependent deacylase, regulates fundamental cellular pathways, including energy substrate metabolism. The current study is designed to better elucidate the role of SIRT5 in the development of heart failure (HF).

Methods

Mice with cardiomyocyte-specific deletion (cSirt5^-/-) or overexpression (cSirt5-Tg) of SIRT5 were generated and subjected to chronic pressure overload by transverse aortic constriction (TAC) or Sham surgery. Cardiac structure and function were assessed by echocardiography, isolated heart perfusions, and histology. MS-based metabolomics and bulk RNA sequencing were used to explore metabolic and molecular signatures.

Results

cSirt5-Tg mice had similar cardiac structure and function compared

SUBMITTER: Byrne NJ 

PROVIDER: S-EPMC12533344 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature