Matrix Metalloproteinase 2 as a Pharmacological Target in Heart Failure

Abstract

Heart failure (HF) is an acute or chronic clinical syndrome that results in a decrease in cardiac output and an increase in intracardiac pressure at rest or upon exertion. The pathophysiology of HF is heterogeneous and results from an initial harmful event in the heart that promotes neurohormonal changes such as autonomic dysfunction and activation of the renin-angiotensin-aldosterone system, endothelial dysfunction, and inflammation. Cardiac remodeling occurs, which is associated with degradation and disorganized synthesis of extracellular matrix (ECM) components that are controlled by ECM metalloproteinases (MMPs). MMP-2 is part of this group of proteases, which are classified as gelatinases and are constituents of the heart. MMP-2 is considered a biomarker of patients with HF with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). The role of MMP-2 in the development of cardiac injury and dysfunction has clearly been demonstrated in animal models of cardiac ischemia, transgenic models that overexpress MMP-2, and knockout models for this protease. New research to minimize cardiac structural and functional alterations using non-selective and selective inhibitors for MMP-2 demonstrates that this protease could be used as a possible pharmacological target in the treatment of HF.

Role of Matrix Metalloproteinases in Musculoskeletal Diseases

“…Baraibar-Churio et al showed that the MMP-10 deficiency causes chronic inflammation in the cardiac and skeletal muscles in aged mdx mice [ 71 ]; thus, suggesting it as a critical therapeutic targe for muscular dystrophy. MMP-2 activity is enhanced in the muscles [ 96 ], and TIMP-1 is increased in the serum and plasma of muscular dystrophy patients [ 97 ]. MMP-10 deficiency has been linked with the progression of severe muscular dystrophy in aged dystrophic mice [ 71 ].…”

PPAR Alpha Activation by Clofibrate Alleviates Ischemia/Reperfusion Injury in Metabolic Syndrome Rats by Decreasing Cardiac Inflammation and Remodeling and by Regulating the Atrial Natriuretic Peptide Compensatory Response

“…In I/R injury, expression of MMP-2 is of particular interest because MMP-2 degrades extracellular matrix substrates including Type IV collagen, laminin, elastin, interstitial fibrillar collagen, and sarcomeric proteins [ 35 , 36 ]. The expression of this zinc-dependent protease is regulated by mechanical signals, inflammatory factors, hormones, and NPs, among other factors; some authors even suggest that MMP-2 can be used as a possible pharmacological target in the treatment of heart failure [ 31 , 36 , 37 , 38 ]. Therefore, we analyzed the expression of MMP-2 in all experimental groups and found that the expression of this enzyme was higher in hearts from MetS rats in sham-operated conditions and under I/R damage without there being changes in the Ct group.…”

Effects of once‐weekly glucagon‐like peptide‐1 receptor agonists on type 2 diabetes mellitus complicated with coronary artery disease: Potential role of the renin‐angiotensin system

“…Ang II stimulates MMP expression in advanced atherosclerotic lesions 43 . MMP2, which is mainly derived from arterial endothelial cells, is one of the most abundant proteases in cardiomyocytes and is considered a biomarker for heart failure and acute coronary syndrome 44,45 . MMP2 mediates Ang II‐induced vascular injury by triggering inflammatory and immune responses and participates in various processes such as ECM degradation, thrombosis and atherosclerotic rupture 46,47 .…”