Insulin Resistance Mediated Changes in Matrix Metalloproteinase Expression and Activity in Diverse Vascular Beds

Abstract

Matrix metalloproteinases (MMP), proteolytic degraders of extracellular matrix proteins, are involved in vascular remodeling. We tested the hypothesis that insulin resistance (IR), a condition that often precedes type II diabetes, differentially changes MMP expression and activity in diverse vascular beds. Aorta, and cerebral and coronary arteries were isolated from Zucker obese (ZO) rats with IR and their lean (ZL) controls. MMP‐9 expression and activity were determined by western blot analysis and zymography, respectively. Levels of the non‐specific tissue inhibitor of matrix metalloproteinase, TIMP‐4, were also evaluated. In the cerebral arteries of ZO rats, the expression of MMP‐9 was 3‐fold (n=6 each, p<.02) greater and accompanied by enhanced activity compared to ZL arteries. In coronary arteries, MMP‐9 expression was higher in ZO than in ZL coronaries (n=5–6, p<.02); however there was no detectable difference in activity. In contrast, MMP‐9 activity was lower in ZO than ZL, although there was no change in protein expression. TIMP‐4 expression remained unchanged in all vascular beds. These results strongly suggest that IR, without additional vascular insult, differentially promotes changes in the expression and activity of MMPs in various peripheral vascular beds. Supported by HL‐065380‐07.