Role of Matrix Metalloproteinase-2 in the Development of Atherosclerosis among Patients with Coronary Artery Disease

Figure 3

Signaling pathways of MMP-2 in atherosclerosis development. Initially, MMP-2 cleaves eNOS or its cofactor, HSP90 to cause endothelial dysfunction and facilitate infiltration of LDL into the intima. Then, MMP-2 expressed by activated platelets promote monocyte transmigration into the intima through endothelial PAR-1 activation. MMP-2 also facilitates oxLDL-induced VSMCs migration to the intima, forming fibrous cap in the atherosclerotic plaque. Last, MMP-2 stimulates fibrous cap degradation and rupture of atherosclerotic plaque via several pathways including Akt-NF-ĸβ pathway which is induced by HNE, and NADPH oxidase pathway which is induced by ANG II and ROS. Akt = activating tyrosine kinase, ANG II, angiotensin II; eNOS, endothelial nitric oxide synthase; HSP90, heat shock protein 90; HNE, hydroxynoneal; LDL, low-density lipoprotein; MMP-2, matrix metalloproteinase-2; MT1-MMP, membrane Type1-matrix metalloproteinase; NAD(P)H, nicotinamide adenine dinucleotide phosphate; NO, nitric oxide; NF-ĸβ, nuclear factor kappa beta; oxLDL, oxidized low density lipoprotein; PAR-1, protease-activated receptor 1; ROS, reactive oxygen species; Sm/Cer/S1P, sphingomyelin/ceramide/sphingosine-1-phosphate; VCAM-1, vascular cell adhesion molecule 1.