Inhibition of matrix metalloproteinase-2 improves endothelial function and prevents hypertension in insulin-resistant rats.

ABSTRACT:

Background and purpose

Insulin resistance is often found to be associated with high blood pressure. We propose that in insulin-resistant hypertension, endothelial dysfunction is the consequence of increased activity of vascular MMP-2. As MMP-2 proteolytically cleaves a number of extracellular matrix proteins, we hypothesized that MMP-2 impairs endothelial function by proteolytic degradation of endothelial NOS (eNOS) or its cofactor, heat shock protein 90 (HSP90).

Experimental approach

We tested our hypothesis in bovine coronary artery endothelial cells and fructose-fed hypertensive rats (FHR), a model of acquired systolic hypertension and insulin resistance.

Key results

Treatment of FHRs with the MMP inhibitor doxycycline, preserved endothelial function as well as pre

SUBMITTER: Nagareddy PR 

PROVIDER: S-EPMC3315042 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature