title: Matrix Metalloproteinase 2 as a Potential Mediator of Vascular Smooth Muscle Cell Migration and Chronic Vascular Remodeling in Hypertension.
abstract: For vascular remodeling in hypertension, it is essential that vascular smooth muscle cells (VSMCs) reshape in order to proliferate and migrate. The extracellular matrix (ECM) needs to be degraded to favor VSMC migration. Many proteases, including matrix metalloproteinases (MMPs), contribute to ECM proteolysis and VSMC migration. Bioactive peptides, hemodynamic forces and reactive oxygen-nitrogen species regulate MMP-2 expression and activity. Increased MMP-2 activity contributes to hypertension-induced maladaptive arterial changes and sustained hypertension. New ECM is synthesized to supply VSMCs with bioactive mediators, which stimulate hypertrophy. MMP-2 stimulates the interaction of VSMCs with newly formed ECM, which triggers intracellular signaling via integrins to induce a phenotypic switch and persistent migration. VSMCs switch from a contractile to a synthetic phenotype in order to migrate and contribute to vascular remodeling in hypertension. MMPs also disrupt growth factors bound to ECM, thus contributing to their capacity to regulate VSMC migration. This review sheds light on the proteolytic effects of MMP-2 on ECM and non-ECM substrates in the vasculature and how these effects contribute to VSMC migration in hypertension. The inhibition of MMP activity as a therapeutic target may make it possible to reduce arterial maladaptation caused by hypertension and prevent the resulting fatal cardiovascular events.
authors.affiliation: Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sx00E3;o Paulo, Ribeirao Preto, Brazil.
authors.forename: V A
authors.initials: VA
authors.lastname: Belo
authors.forename: Danielle A
authors.initials: DA
authors.lastname: Guimarães
authors.forename: Michele Mazzaron
authors.initials: MM
authors.lastname: Castro
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002465:Cell Movement; D048430:Cell Shape; D002908:Chronic Disease; D005109:Extracellular Matrix / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006973:Hypertension / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology* / Q000473:pathology; D010641:Phenotype; D015398:Signal Transduction; D066253:Vascular Remodeling
chemical_list: D020778:Matrix Metalloproteinase 2