Overexpression of the angiotensin AT1 receptor in mouse cardiac myocytes resulted in massive atrial enlargement, bradycardia, heart block, and early postnatal lethality.
Does overexpression of the AT1a receptor transgene in mouse myocardium induce cardiac myocyte growth and alter electrical conduction?
Direct activation of AT1 receptor signaling in cardiac myocytes in vivo is sufficient to induce cardiac myocyte growth, alter electrical conduction, and cause early mortality.
Absolute Event Rate: 58.1% vs 27.2%
p-value: p=<0.01
Previous studies have suggested that angiotensin II (Ang II) modulates cardiac contractility, rhythm, metabolism, and structure. However, it is unclear whether the cardiac effects are due to direct actions of Ang II on the myocardium or if they are due to secondary effects mediated through the hemodynamic actions of Ang II. In this study, we used the alpha-myosin heavy chain (alphaMHC) promoter to generate transgenic mice overexpressing angiotensin II type 1 (AT1a) receptor selectively in cardiac myocytes. The specificity of transgene expression in the transgenic offspring was confirmed by radioligand binding studies and reverse transcription-PCR. The offspring displayed massive atrial enlargement with myocyte hyperplasia at birth, developed significant bradycardia with heart block, and died within the first weeks after birth. Thus, direct activation of AT1 receptor signaling in cardiac myocytes in vivo is sufficient to induce cardiac myocyte growth and alter electrical conduction.
Hein et al. (1997) studied Myocardial AT1 receptor overexpression. aMHC-AT1 transgene vs. Wild-type littermates was evaluated on Heart weight (mg) (p=<0.01). Overexpression of the angiotensin AT1 receptor in mouse cardiac myocytes resulted in massive atrial enlargement, bradycardia, heart block, and early postnatal lethality.