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MiR-203 improves cardiac dysfunction by targeting PARP1-NAD+ axis in aging murine.


ABSTRACT: Heart aging is a prevalent cause of cardiovascular diseases among the elderly. NAD+ depletion is a hallmark feature of aging heart, however, the molecular mechanisms that affect NAD+ depletion remain unclear. In this study, we identified microRNA-203 (miR-203) as a senescence-associated microRNA that regulates NAD+ homeostasis. We found that the blood miR-203 level negatively correlated with human age and its expression significantly decreased in the hearts of aged mice and senescent cardiomyocytes. Transgenic mice with overexpressed miR-203 (TgN (miR-203)) showed resistance to aging-induced cardiac diastolic dysfunction, cardiac remodeling, and myocardial senescence. At the cellular level, overexpression of miR-203 significantly prevented D-gal-induced cardiomyocyte senescence and mitochondrial damage, while miR-203 knockdown aggravated these effects. Mechanistically, miR-203 inhibited PARP1 expression by targeting its 3'UTR, which helped to reduce NAD+ depletion and improve mitochondrial function and cell senescence. Overall, our study first identified miR-203 as a genetic tool for anti-heart aging by restoring NAD+ function in cardiomyocytes.

SUBMITTER: Zhao L 

PROVIDER: S-EPMC10928583 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Heart aging is a prevalent cause of cardiovascular diseases among the elderly. NAD<sup>+</sup> depletion is a hallmark feature of aging heart, however, the molecular mechanisms that affect NAD<sup>+</sup> depletion remain unclear. In this study, we identified microRNA-203 (miR-203) as a senescence-associated microRNA that regulates NAD<sup>+</sup> homeostasis. We found that the blood miR-203 level negatively correlated with human age and its expression significantly decreased in the hearts of ag  ...[more]

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