Pcsk6, short for proprotein convertase subtilisin/kexin type 6, is a calcium-dependent serine proteinase. It regulates the proteolytic activity of various precursor proteins, facilitating protein maturation. It has been implicated in several biological processes including those related to cardiovascular, pulmonary, and nervous systems, as well as in colitis and membranous nephropathy [4,5,6].

In cardiovascular research, Pcsk6-deficient mice showed increased flow-mediated outward arterial remodeling and reduced medial contractility in response to increased blood flow, suggesting its role in vascular remodeling [7]. In the context of cardiac remodeling after myocardial infarction, Pcsk6 was identified as a key player. Hypoxia-induced secretion analysis in cardiomyocytes showed up-regulation of Pcsk6, and its overexpression in mice led to increased collagen expression, cardiac fibrosis, and decreased left ventricular function [1]. In doxorubicin-induced cardiotoxicity, overexpression of Pcsk6 protected cardiac function by promoting autophagy through the SIRT1/FOXO3a pathway [2]. In cardiomyocyte senescence, Pcsk6 deficiency promoted senescence via Ddit3-mediated ER stress [3].

In conclusion, Pcsk6 is crucial for maintaining normal physiological functions in multiple systems. Mouse models, especially gene knockout models, have been instrumental in revealing its role in diseases such as cardiac remodeling after myocardial infarction, doxorubicin-induced cardiotoxicity, and cardiomyocyte senescence, providing potential therapeutic targets for these conditions.