title: 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.
authors.affiliation: Department of Biochemistry, School of Translational Medicine, University of Alberta, Edmonton, Alta., Canada.
authors.forename: Evan
authors.initials: E
authors.lastname: Berry
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Bosonea
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernandez-Patron
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000072199:ADAM12 Protein; D000072198:ADAM17 Protein; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002319:Cardiovascular System / Q000187:drug effects / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D006331:Heart Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000627:therapeutic use; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D000959:Antihypertensive Agents; D008074:Lipoproteins; D061965:Matrix Metalloproteinase Inhibitors; D008565:Membrane Proteins; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human; D020782:Matrix Metalloproteinases; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human