Overexpression of angiotensin AT 1 receptor transgene in the mouse myocardium produces a lethal phenotype associated with myocyte hyperplasia and heart block

• DOI: 10.1073/pnas.94.12.6391
• Publication Date: 2002-07-26T14:43:20Z
• Authors: Lutz Hein; Mary E. Stevens; Gregory S. Barsh; Richard E. Pratt; Brian K. Kobilka; Victor J. Dzau
• Keywords: Cardiac myocyte; Contractility

Previous studies have suggested that angiotensin II (Ang II) modulates cardiac contractility, rhythm, metabolism, and structure. However, it is unclear whether the effects are due to direct actions of Ang on myocardium or if they secondary mediated through hemodynamic II. In this study, we used α-myosin heavy chain (αMHC) promoter generate transgenic mice overexpressing type 1 (AT 1a ) receptor selectively in myocytes. The specificity transgene expression offspring was confirmed by radioligand binding reverse transcription–PCR. displayed massive atrial enlargement with myocyte hyperplasia at birth, developed significant bradycardia heart block, died within first weeks after birth. Thus, activation AT signaling myocytes vivo sufficient induce growth alter electrical conduction.