Equibiaxial stretching of adult ventricular myocytes increased apoptosis by 7.6-fold at 24 hours, a process coupled with angiotensin II release and p53 activation.
Equibiaxial stretch induces adult myocyte apoptosis through angiotensin II release and p53 activation, a process that can be prevented by AT1 receptor blockade.
Effect estimate: 7.6-fold increase
Absolute Event Rate: 17.6% vs 2.33%
p-value: p=<0.001
Physical forces activate apoptosis and gene expression, but the mechanism is unknown. For this purpose, adult myocytes were stretched in an equibiaxial stretch apparatus and the magnitude of cell death was examined 4 and 24 h later. The possibility of stretch-mediated activation of p53 and p53-dependent genes was evaluated at 30 min, 2, 4, 8, and 24 h. Myocyte apoptosis increased by 4.4- and 7.6-fold at 4 and 24 h after stretch. p53 binding to the promoter of angiotensinogen, AT1 receptor, and Bax also increased. Expression of angiotensinogen, AT1 receptor, p53, and Bax increased and Bcl-2 decreased in stretched myocytes. The changes in AT1 receptor, p53, Bax, and Bcl-2 became more apparent with the duration of stretch. Angiotensin II concentration in the medium increased at 10 min, reaching maximal levels at 1 and 20 h. The AT1 blocker, losartan, abolished apoptosis in stretched myocytes. Myocyte volume was not influenced by stretch. In conclusion, stretch-mediated release of angiotensin II is coupled with apoptosis and the activation of p53 which may be responsible for the prolonged upregulation of the local renin-angiotensin system and the increased susceptibility of myocytes to undergo apoptosis.
Leri et al. (1998) studied Myocyte apoptosis. Equibiaxial stretch vs. Nonstretched myocytes was evaluated on Myocyte apoptosis at 24 hours (TdT assay) (7.6-fold increase, p=<0.001). Equibiaxial stretching of adult ventricular myocytes increased apoptosis by 7.6-fold at 24 hours, a process coupled with angiotensin II release and p53 activation.