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Delineation of the effects of angiotensin type 1 and 2 receptors on HL-1 cardiomyocyte apoptosis

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Abstract

Angiotensin II (Ang II) exerts its effects by activating its receptors, primarily type 1 (AT1R) and type 2 (AT2R). While the role of AT1R activation in cardiomyocyte physiology is well known, the role of AT2R in cardiomyocyte apoptosis remains controversial. To define the precise role of AT1R and AT2R in this process, we transfected HL-1 cardiomyocytes with AT1R or AT2R cDNA, and examined markers of apoptosis. We found that AT1R overexpression was associated with upregulation of endogenous AT2R expression, but AT2R overexpression did not affect endogenous AT1R expression. Caspase-3 staining indicated that overexpression of AT1R as well as AT2R resulted in cardiomyocyte apoptosis with appropriate alterations in annexin V, Bax and Bcl2 expression. Overexpression of AT1R and AT2R markedly increased IL-1β (AT2R>AT1R), iNOS (AT2R>AT1R) and eNOS expression. AT2R-induced cell apoptosis could be blocked by the iNOS selective inhibitor 1,400 W, and did not require exogenous Ang II. These findings suggest that AT2R overexpression induces cardiomyocyte apoptosis, most likely via iNOS upregulation. AT1R-mediated cardiomyocyte apoptosis may be partially mediated by upregulation of endogenous AT2R.

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Authors and Affiliations

  1. Division of Cardiology, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, AR, USA

    Xianwei Wang, Jingjun Lu, Magomed Khaidakov, Sona Mitra, Zufeng Ding, Tanu Goyal & Jawahar L. Mehta

  2. Department of Emergency Medicine, Renmin Hospital of Wuhan University, Wuhan, China

    Jingjun Lu

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  1. Xianwei Wang
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  2. Jingjun Lu
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  3. Magomed Khaidakov
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  4. Sona Mitra
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  5. Zufeng Ding
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  6. Tanu Goyal
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  7. Jawahar L. Mehta
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Correspondence to Jawahar L. Mehta.

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X. Wang and J. Lu equally contributed to this paper.

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Wang, X., Lu, J., Khaidakov, M. et al. Delineation of the effects of angiotensin type 1 and 2 receptors on HL-1 cardiomyocyte apoptosis. Apoptosis 17, 908–915 (2012). https://doi.org/10.1007/s10495-012-0721-6

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  • DOI: https://doi.org/10.1007/s10495-012-0721-6

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