Pioglitazone Improves Matrix Metalloproteinase–9 Activity in Plasma and Vitreous in Spontaneously Hypertensive Hyperlipidemic Rats

Abstract

Purpose: : Spontaneously hypertensive hyperlipidemic rats (SHHR) are developed for the early stage model of atherosclerosis (Clin. Exp. Pharmacol. Physiol. 2003 30:537–44). We reported previously that matrix metalloproteinase–9 (MMP–9) activity in vitreous increased in SHHR fed on normal diet compared with Sprague–Dawley (SD) rats (IOVS. 2005 46:1008–B982). MMP–9 plays an important role in atherosclerosis and retinal degeneration. Pioglitazone, Peroxisome Proliferator–Activated Receptor gamma (PPAR–gamma) agonists, is already showed to inhibit MMP–9 activity in vitro. The aim of this study is to investigate effects of Pioglitazone on plasma and vitreous MMPs in SHHR fed on a high fat diet with 15% sucrose solution (HFDS).

Methods: : Five months old male SHHR and SD rats were administered N^G–nitro L–arginine methyl ester (L–NAME) for one month, then HFDS ad libitum for two months. Effects of Pioglitazone on plasma and vitreous MMPs activities in HFDS treated SHHR and SD rats were examined by gelatine zymography after subcutaneous injection of Pioglitazone for two months.

Results: : Both plasma and vitreous MMP–9 activities were significantly increased in these HFDS treated SHHR and SD rats compared with non–treated SHHR and SD rats, respectively. In Pioglitazone treated HFDS rats, plasma and vitreous MMP–9 activities were returned to their control levels. MMP–2 activities in plasma and vitreous had little changes among these model rats.

Conclusions: : These results suggest that Pioglitazone may improve retinal degeneration by inhibiting MMP–9 activity.

Keywords: vitreous • protein structure/function • retina