• Hypertension · Jun 2014

    Effects of cardiac overexpression of the angiotensin II type 2 receptor on remodeling and dysfunction in mice post-myocardial infarction.

    • Jiang Xu, Ying Sun, Oscar A Carretero, Liping Zhu, Pamela Harding, Edward G Shesely, Xiangguo Dai, Nour-Eddine Rhaleb, Edward Peterson, and Xiao-Ping Yang.
    • Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, E&R 7081, 2799 W Grand Boulevard, Detroit, MI 48202-2689. xpyang1@hfhs.org.
    • Hypertension. 2014 Jun 1;63(6):1251-9.

    AbstractThe activation of angiotensin II type 2 receptor (AT2R) has been considered cardioprotective. However, there are controversial findings regarding the role of overexpressing AT2R in the heart. Using transgenic mice with different levels of AT2R gene overexpression in the heart (1, 4, or 9 copies of the AT2R transgene: Tg1, Tg4, or Tg9), we studied the effect of AT2R overexpression on left ventricular remodeling and dysfunction post-myocardial infarction (MI). Tg1, Tg4, Tg9, and their wild-type littermates were divided into (1) sham MI, (2) MI plus vehicle, and (3) MI plus AT2R antagonist. Treatments were started 4 weeks after MI and continued for 8 weeks. AT2R protein and mRNA expression in the heart was significantly increased in transgenic mice, and the increase positively correlated with copies of the transgene. AT1R protein and mRNA expression remained unchanged in Tg1 and Tg4 but slightly increased in Tg9 mice. Systolic blood pressure and cardiac phenotypes did not differ among strains under basal conditions. MI caused myocardial hypertrophy, interstitial fibrosis, ventricular dilatation, and dysfunction associated with increased protein expression of Nox2 and transforming growth factor β1. These pathological responses were diminished in Tg1 and Tg4 mice. Moreover, the protective effects of AT2R were abolished by AT2R antagonist and also absent in Tg9 mice. We thus conclude that whether overexpression of AT2R is beneficial or detrimental to the heart is largely dependent on expression levels and possibly via regulations of Nox2 and transforming growth factor β1 signaling pathways.

      Pubmed     Free full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…

Want more great medical articles?

Keep up to date with a free trial of metajournal, personalized for your practice.
1,694,794 articles already indexed!

We guarantee your privacy. Your email address will not be shared.