Abstract 322: Imbalance Between MMP-2 and TIMP-4 Associated With Oxidative Stress Contributes to Temporal Renovascular Hypertension-Induced Cardiac Hypertrophy

Abstract

Imbalanced matrix metalloproteinase (MMP) activity is associated with left ventricular hypertrophy (LVH). Increased reactive oxygen species (ROS) formation enhances MMP activity and decrease tissue inhibitor of MMP (TIMP) activity. We examined the temporal relationship between ROS, MMP-2, and TIMP-4 levels in the heart during the progression of LVH in two-kidney, one-clip (2K1C) hypertension. Sham or 2K1C hypertensive rats were studied after 15, 30, and 75 days of hypertension, and the results are expressed as % of values found in corresponding sham animals at each time point. Systolic blood pressure increased with time in 2K1C rats: 167±3, 201±1, and 203±2 mmHg after 15, 30, and 75 days of hypertension (all P<0.05). Hypertension induced LVH in a time-dependent manner (P<0.05). Collagen deposition increased by 250±23%, 213±20% and 235±16% in 2K1C rats, respectively, after 15, 30, and 75 days of hypertension; all P<0.05 vs. respective sham). Cardiac MMP-2 levels increased from 13±1 (sham) to 19±2, 17±1, and 20±2 arbitrary units (AU) after 15, 30, and 75 days of hypertension, respectively (all P<0.05 vs. sham). Cardiac TIMP-4 levels increased by 325±68% (P<0.05) only after 75 days of hypertension. Cardiac gelatinolytic activity increased by 129±4%, 150±6%, and 152±6% after 15, 30, and 75 of hypertension, respectively (all P<0.05 vs. sham). Cardiac ROS levels increased by 137±5%, 154±15%, and 130 ±10% after 15, 30, and 75 days of hypertension, respectively (all P<0.05 vs. sham). These results indicate that LVH in is an early process associated with imbalanced MMP-2 and TIMP-4 levels in renovascular hypertension, thus resulting in increased gelatinolytic activity and fibrosis, which may be due to oxidative stress.