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Annals of Clinical & Laboratory Science 36:88-95 (2006)
© 2006 Association of Clinical Scientists

Apoptosis in Pressure Overload-Induced Cardiac Hypertrophy Is Mediated, in Part, by Adenine Nucleotide Translocator-1

Tao Hang1,2, Zhaoqi Huang1, Shisen Jiang2, Jianbin Gong2, Chunhui Wang2, Dujiang Xie2 and Hailing Ren2
1 School of Life Science, Nanjing University, and 2 Department of Cardiology, Jinling Hospital, Nanjing, People’s Republic of China

Address correspondence to Tao Hang, Ph.D., Department of Cardiology, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, P.R.China; tel 86 25 8086 0880; fax 86 25 8459 5315; e-mail: njht1976{at}yahoo.com.cn.

This study explored the role of adenine nucleotide translocator-1 (ANT1) in cardiomyocyte apoptosis during left ventricular hypertrophy (LVH) that developed in response to pressure overload. Pressure overload was induced surgically in 21 male Sprague-Dawley rats by thoracic aortic constriction at 12 weeks of age. An equal number of sham-operated, age-matched male rats served as controls. Aortic blood pressure (ABP), LVH, myocardial apoptosis index (MAI), and ANT1 mRNA expression were quantified in 7 subgroups of 3 treated and 3 control rats that were killed, respectively, at 1, 2, 4, 7, 14, 21, or 30 days post-surgery. Compared to controls, ABP increased gradually throughout the study in the treated rats with aortic coarctation; LVH did not develop significantly until 4 days post-surgery and increased progressively afterwards. The myocardial apoptosis index (assayed by TUNEL-labeling) increased immediately post-surgery, reached a plateau from 4 to 7 days, and then declined rapidly; apoptosis was undetectable throughout the study in cardiomyocytes of control rats. In treated rats, the expression of ANT1 mRNA in myocardium was up-regulated at 4 days, peaked at 7 days, and returned to control levels at 14 days post-surgery. These findings suggest that (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 is mediated, in part, by ANT1.

Keywords: adenine nucleotide translocator-1, apoptosis, cardiac hypertrophy, hypertension






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