Acta biochimica et biophysica SinicaSep 14, 2026

piR-45962 increases self-destructive cell death in aged heart injury by affecting a specific cell signaling pathway

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Sep 15, 2026

Abstract

The upregulation of piR-45962 is significantly associated with apoptosis and autophagy in myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion injury is linked to age and contributes to poor outcomes after heart attacks.
Ischemic and hypoxic stress activates both programmed cell death (apoptosis) and a cellular recycling process (autophagy) in heart cells.
Piwi-interacting RNAs, specifically piR-45962, may play a role in regulating these processes during injury.
Mechanistic studies indicate that piR-45962 targets a protein called HNRNPH1, which is involved in controlling apoptosis.
HNRNPH1 may interact with another protein, GATA5, potentially worsening cell death through autophagy.
The study suggests a new regulatory pathway (piR-45962-HNRNPH1-GATA5) that may influence heart damage in older individuals.

Simplified

Myocardial ischemia-reperfusion (I/R) injury is a significant contributor to poor prognosis after myocardial infarction, and the degree of irreversible myocardial damage is closely related to age. In I/R injury, ischemic and hypoxic stress triggers the coordinated activation of apoptosis and autophagy in cardiomyocytes. Although Piwi-interacting RNAs (piRNAs) have been implicated in the regulation of both apoptosis and autophagy, their specific roles and particularly their functional integration in governing this dual cell death response during I/R injury remain poorly understood. Using left anterior descending coronary artery ligation in an aging rat model and a D-galactose-induced rat cardiomyocyte line to construct an aging cardiomyocyte model, we investigate the cell apoptosis and autophagy following reperfusion injury both in vitro and in vivo. The present study focuses on the upregulation of piR-45962 in reperfusion injury in vitro and in vivo, and the indicators of apoptosis and autophagy are significantly different. Mechanistic research of piR-45962 shows that heterogeneous nuclear ribonucleoprotein 1 (HNRNPH1) is a target protein for piR-45962, and as an RNA-binding protein implicated in apoptotic regulation, HNRNPH1 could interact with GATA binding protein 5 (GATA5) to exacerbate autophagic apoptosis. Together, our results reveal the mechanism by which piR-45962 downregulates GATA5 expression through upregulation of HNRNPH1, thereby establishing a novel piR-45962-HNRNPH1-GATA5 regulatory axis that contributes to aged myocardial injury during I/R.

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piR-45962 increases self-destructive cell death in aged heart injury by affecting a specific cell signaling pathway

Abstract

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