Apoptosis and expression of uncoupling protein-2 in pressure overload-induced left ventricular hypertrophy

Abstract

Objective — To explore the possible role of uncoupling protein-2 (UCP2) in cardiomyocyte apoptosis in pressure overload-induced left ventricular hypertrophy (LVH).

Methods and results — Pressure overload was developed in 21 Sprague-Dawley rats by thoracic aortic constriction at 12 weeks of age.An equal number of sham-operated, age-matched rats served as controls.Aortic blood pressure (ABP), LVH, myocardial apoptosis index (MAI), and UCP2 mRNA expression were quantified in 7 subgroups of 3 treated and 3 control rats that were killed, at 1,2, 4, 7, 14, 21, or 30 days post-surgery, respectively., Compared to controls, ABP increased gradually throughout the study in the treated rats;LVH did not develop significantly until 4 days after surgery and increased progressively afterwards. The MAI increased immediately after surgery, reached a plateau from 4 to 7 days, and then declined rapidly;apoptosis was undetectable throughout the study in the cardiomyocytes of the control rats. In treated rats, the expression of UCP2 mRNA in myocardium was upregulated at 4 days, and developed progressively to the end of the experiment.

Conclusions — (i) Apoptosis of cardiomyocytes is an important regulatory mechanism that is involved in the cardiac adaptive response to pressure overload, and (ii) the apoptosis of cardiomyocytes may be suppressed, in part, by UCP2.

Key Words:

• uncoupling protein-2
• apoptosis
• left ventricular hypertrophy
• pressure overload