Matrix Metalloproteinase 2 as a Potential Mediator of Vascular Smooth Muscle Cell Migration and Chronic Vascular Remodeling in Hypertension

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 caReceived: June 1, 2015 Accepted after revision: October 10, 2015 Published online: January 6, 2016 Prof. Dr. Michele Mazzaron de Castro Department of Pharmacology, Faculty of Medicine University of São Paulo Av. Bandeirantes, 3900, 14049-900 Ribeirao Preto, SP (Brazil) E-Mail castro @ fmrp.usp.br © 2016 S. Karger AG, Basel 1018–1172/16/0524–0221$39.50/0