Legumain in cardiovascular diseases

Abstract

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, having become a global public health problem, so the pathophysiological mechanisms and therapeutic strategies of CVDs need further study. Legumain is a powerful enzyme that is widely distributed in mammals and plays an important role in a variety of biological processes. Recent research suggests that legumain is associated with the occurrence and progression of CVDs. In this review, we provide a comprehensive overview of legumain in the pathogenesis of CVDs. The role of legumain in CVDs, such as carotid atherosclerosis, pulmonary hypertension, coronary artery disease, peripheral arterial disease, aortic aneurysms and dissection, is discussed. The potential applications of legumain as a biomarker of these diseases are also explored. By understanding the role of legumain in the pathogenesis of CVDs, we aim to support new therapeutic strategies to prevent or treat these diseases.

Keywords: aortic disease; atherosclerosis; cardiovascular disease; coronary artery disease; legumain.

FIGURE 1

Illustration of the legumain pathway. ①LGMN could promote ECM degradation by activation of proMMP-2, processing of cathepsins or by direct proteolysis of ECM components like fibronectin. Meanwhile, LGMN promotes ECM remodeling by activating the MMP-2/TGF-β1 signaling. ②LGMN is involved in regulating the recruitment and infiltration of inflammatory cells, as well as regulating the expression of intracellular inflammatory factors. ③LGMN promotes clearance and degradation of apoptotic cardiomyocytes by efferocytosis. ④LGMN promotes macrophage uptake of ox-LDL to form lipid droplets by increasing SR-A expression. ⑤LGMN binds and blocks integrin αvβ3, thereby attenuating Rho GTPase activation and downregulating VSMC differentiation markers. ER: endoplasmic reticulum; ACAT1: acyl-coenzyme A: cholesterol acyltransferase-1; NCEH: neutral cholesterol ester hydrolase; SR-A: scavenger receptor class A; ox-LDL: oxidized low-density lipoprotein; α-SMA: α–smooth muscle actin; AM22α: smooth muscle 22α; CNN1: calponin 1; TGF-β: transforming growth factor-β; PASMC: pulmonary artery smooth muscle cell; MARCO: macrophage receptor with collagenous structure; IL: Interleukin; MPO: myeloperoxidase.