Insights into the Activity, Differential Expression, Mutual Regulation, and Functions of Matrix Metalloproteinases and A Disintegrin and Metalloproteinases in Hypertension and Cardiac Disease

Abstract

Hypertensive cardiac disease is a major cause of death worldwide. Causative factors of hypertension include environmental stressors, genetic predisposition, and common morbidities of lipid metabolism such as obesity and diabetes. These factors pathologically elevate the systemic production of vasoconstrictive G-protein-coupled receptor agonists. Pathological concentrations of these agonists upregulate the gene expression and proteolytic activity of matrix metalloproteinases (MMPs) and A disintegrin and metalloproteinases (ADAMs). Among the metalloproteinases that act in concert with other mediators to elevate the systemic blood pressure and to modulate the development of cardiovascular hypertrophy and fibrosis processes are MMP-2, MMP-7, ADAM-12, and ADAM-17. This review offers insights into the activity, differential expression, mutual regulation, and functions of these metalloproteinases. We further review evidence linking them to transcription factors, carrier proteins, and receptors for lipids. The emerging links between metalloproteinases and lipids are intriguing and suggest new therapeutic targets in hypertensive cardiac disease.