Alterations in Protein P53 Expression During the Development of Pressure Overload-Induced Left Ventricular Hypertrophy in Rats

ABSTRACT

The relation between myocardial structural and functional changes and p53 proteins during the development of left ventricular hypertrophy (LVH) has not yet been reported. The purpose of this study was to determine whether p53 protein expression is altered during development of LVH, induced by pressure overload.

LVH was induced in 80 male Wistar adult rats by abdominal aortic banding (AAB) and was monitored at the 10^th, 15^th, 20^th, 25^th, 35^th and 45^th post-operation days by echocardiography and validated by postmortem examination. Sham operated (SO) rats (n=60) went the same operation without banding. The expression of p53 protein in the nuclear and cytoplasmic extracts from left ventricular tissue from AAB and SO rats were analyzed by immunoblotting at each of the pointed days.

Relative to SO, echo-left ventricular mass-to-tibia length (LVM/TL) ratio in AAB increased progressively on the 10^th and the 15^thday. On the 20^th day we observed a short lasting regression of LVH, followed by a new marked increase on the 25^th and 35^th day; then there was presented a plateau. Relative to SO the changes in LV%FS (77% ± 2.2 %) in AAB rats remained at the same level throughout the studied period without significant differences in body weight or tibia length (TL). Results from echocardiography were validated by necropsy. Echo LVM/TL correlated significantly with actual heart weight-to-tibia length ratio (r=0.69, P< 0.0001, n=140).

The level of p53 protein expression in the nuclear extracts from LV tissues obtained from AAB rats increased significantly by 77%, 78%, 35% and 63% at day 10^th, 20^th, 35^th and 45^th, respectively compared with SO, and returned to SO levels by day 15^thand 25^th post-operation. The highest level of p53 protein in the nuclear extracts from LV tissues obtained from AAB rats was determined on 20^th day concomitant with significant reduction of the actual heart mass in the group with AAB rats, compared with the same groups on the other days. In the cytozol the expression of p53 was always higher in the SO, compared with AAB groups. Furthermore, the level ofp53 protein in the nuclear extracts from AAB rats significantly correlated with the actual heart weight during the studied period (r= -0.59, P< 0.0001, n=60).

Following the development of LVH over a relatively long period of time and providing the changes in short intervals, it was found a short lasting regression during ongoing pressure overload concomitant with significantly increased expression of p53 protein in the nuclear extracts from AAB rats.

This study adds new important concepts for the time dependency of LVH and suggests that p53 protein may modulate the adaptive growth of pressure overload induced LVH.

Keywords:

• protein p53
• left ventricular hypertrophy
• rats