DNA-binding Protein A Inhibitor Improves Cardiac Function After Acute Myocardial Infarction by the Platelet-derived...

The present study investigates the regulatory role and underlying mechanisms of DbpA in cardiac function following acute myocardial infarction (AMI).

In Vitro Studies: Primary rat cardiomyocytes and vascular smooth muscle cells (VSMCs) were isolated and characterized using established protocols. Flow cytometry quantitatively assessed apoptosis rates and cell cycle distribution following modulation of the PDGF-MAPK-DbpA pathway. Western blot analysis evaluated the expression levels of pathway components (PDGF, MAPK, DbpA).

An AMI rat model was established through coronary artery ligation. Following pharmacological inhibition of PDGF and MAPK signaling, we assessed cardiac remodeling indices, cardiac function parameters, histopathology, cardiomyocyte apoptosis, and pathway protein expression (PDGF, MAPK, DbpA).

In Vitro Studies: Compared with hypoxia-treated controls, both PDGFinhibitor and MAPK-inhibitor treatments resulted in a significant reduction in apoptosis of cardiomyocytes and VSMCs, markedly promoted cellular proliferation, and downregulated protein expression of PDGF, MAPK, and DbpA pathway components.

Relative to ischemia-reperfusion controls, PDGF-inhibitor, MAPKinhibitor, and DbpA-inhibitor interventions consistently yielded improved cardiac functional parameters, reduced myocardial necrosis, and significantly suppressed PDGF, MAPK, and DbpA protein expression.

DbpA serves as a pivotal regulator in the PDGF-MAPK-DbpA axis, modulating both acute pathological processes and long-term outcomes following myocardial infarction.

This study demonstrates that the DbpA inhibitor exerts cardioprotective effects by suppressing cellular apoptosis, promoting proliferation, reducing the heart weight/body weight ratio and left ventricular mass index, limiting necrotic areas, enhancing cardiac functional parameters, and improving myocardial tissue architecture. These beneficial effects are mediated through modulation of the PDGFMAPK-DbpA signaling pathway. Our findings suggest that DbpA represents a promising therapeutic target for preserving cardiac function after AMI and a potential candidate molecule for myocardial protection in acute myocardial infarction.