Title:Inhibition of Matrix Metalloproteinases (MMPs) as a Potential Strategy to Ameliorate Hypertension-Induced Cardiovascular Alterations
Volume: 14
Issue: 3
Author(s): Michele M. Castro and Jose E. Tanus-Santos
Affiliation:
Keywords:
Cardiovascular remodeling, doxycycline, hypertension, matrix metalloproteinases, oxidative stress, reninangiotensin-aldosterone system, Arterial hypertension, tissue inhibitors of metalloproteinases (TIMPs), VSMCs and extracellular matrix
Abstract: A group of proteases, the matrix metalloproteinases (MMPs) are well known for their capacity to degrade extracellular
matrix (ECM) proteins. Particularly MMP-2 and MMP-9 contribute to the degradation and reorganization of
the ECM components and are involved in the pathophysiology of cardiovascular remodeling. Imbalanced MMP activity
promotes vascular smooth muscle cells and migration and proliferation and endothelial dysfunction, thus resulting in increased
cardiovascular stiffness and hypertrophy. Furthermore, MMP-2 cleaves non-ECM protein substrates including
cellular receptors and intracellular proteins, thus causing cardiac and vascular dysfunction. It is now becoming clear that
increased MMP activity promotes long-lasting cardiovascular structural and functional alterations in both experimental
and clinical hypertension, and this alteration may contribute to sustained hypertension and its complications. Other pathogenic
mechanisms including activation of the renin-angiotensin-aldosterone system and oxidative stress activate and upregulate
MMPs. Therefore, MMP inhibition may prevent the deleterious consequences of hypertension to the cardiovascular
system. This review article will focus on growing evidence supporting the relevance of MMPs in hypertension and the
effects of MMP inhibitors. Particularly, the effects of doxycycline used as a non selective MMP inhibitor in experimental
and clinical studies will be discussed.
