Neuropeptide Y promotes myocardial fibrosis post myocardial infarction reperfusion through Neuropeptide Y receptor type 1.

Although the treatment of ischemic heart disease is becoming increasingly mature, the role of neuropeptide Y (NPY) in the pathophysiology after reperfusion still remains remains unanswered. In our study, we used a mouse model of myocardial ischemia/reperfusion (I/R) injury and demonstrated significant upregulation of NPY and its receptor NPYR1 after reperfusion. Over-expression of NPYR1exacerbates cardiac remodeling, manifested as worsening myocardial fibrosis (p < 0.01) and impaired left ventricular ejection fraction. On the contrary, NPYR1 knockdown weakened fibrosis response and improved cardiac function recovery. These findings were confirmed in HL-1 cell line subjected to hypoxia/reoxygenation model, where fibrotic markers of cardiomyocyte were similarly influenced by NPYR1 modulation. Our research findings indicate that NPY/NPYR1 signaling plays a pivotal role in maladaptive cardiac remodeling post I/R injury and is a promising therapeutic target for alleviating excessive fibrosis.