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Overexpression of Angiotensin II type 2 receptor (AT2R) in neonatal cardiomyocytes induces apoptosis
Author(s) -
Qi Yanfei,
Li Hongwei,
Mecca Adam,
Shenoy Vinayak,
Sumners Colin,
Katovich Michael
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1238.18
Subject(s) - tunel assay , apoptosis , receptor , angiotensin ii , signal transduction , myocyte , microbiology and biotechnology , endocrinology , medicine , biology , chemistry , biochemistry
In vitro experiments suggest that AT2R is involved in apoptosis of fibroblasts, neurons, and endothelial cells. These apoptotic effects are elicited by either Ang II stimulation or constitutive activation of the AT2 receptor. However, the apoptotic effects of AT2R in cardiomyocytes have not been elucidated. Therefore, we investigated the effects of AT2R overexpression in neonatal rat cardiomyocytes. Neonatal cardiomyocytes were isolated from 5‐day old SD rat pups. An AT2R recombinant adenovirus, Ad5‐CMV‐AT2R‐EGFP, was used to overexpress AT2R. At 48 hours post transduction, apoptosis was evaluated by a deoxynucleotidyltransferase‐mediated dUTP‐biotin nick end labeling (TUNEL) assay (for in situ detection of apoptotic cells). Apoptosis was quantified by percentage of positive TUNEL stained area using ImageJ software. Apoptosis was significantly higher in the AT2R overexpressed cardiomyocytes (2.24 %) compared to both PBS (0.46%) and GFP (0.32%) control groups (P<0.001). A decrease in cell density was evident only in the AT2R overexpressed group after 96 hours of viral transduction compared to the PBS and GFP control groups. We conclude that this decrease in cardiac myocyte density is likely due to constitutive pro‐apoptotic signaling via the AT2R.