Cardiac Function and Architecture Are Maintained in a Model of Cardiorestricted Overexpression of the Prorenin-Renin ReceptorReportar como inadecuado




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The prorenin-renin receptor, PRR has been claimed to be a novel element of the renin-angiotensin system RAS. The function of PRR has been widely studied in renal and vascular pathology but the cardio-specific function of PRR has not been studied in detail. We therefore generated a transgenic mouse Tg with cardio-restricted PRR overexpression driven by the alpha-MHC promotor. The mRNA expression of PRR was ∼170-fold higher P<0.001 and protein expression ∼5-fold higher P<0.001 in hearts of Tg mice as compared to non-transgenic wild type, Wt littermates. This level of overexpression was not associated with spontaneous cardiac morphological or functional abnormalities in Tg mice. To assess whether PRR could play a role in cardiac hypertrophy, we infused ISO for 28 days, but this caused an equal degree of cardiac hypertrophy and fibrosis in Wt and Tg mice. In addition, ischemia-reperfusion injury was performed in Langendorff perfused isolated mouse hearts. We did not observe differences in parameters of cardiac function or damage between Wt and Tg mouse hearts under these conditions. Finally, we explored whether the hypoxia sensing response would be modulated by PRR using HeLa cells with and without PRR overexpression. We did not establish any effect of PRR on expression of genes associated with the hypoxic response. These results demonstrate that cardio-specific overexpression of PRR does not provoke phenotypical differences in the heart, and does not affect the hearts’ response to stress and injury. It is concluded that increased myocardial PRR expression is unlikely to have a major role in pathological cardiac remodeling.



Autor: Hasan Mahmud, Wellington Mardoqueu Candido, Linda van Genne, Inge Vreeswijk-Baudoin, Hongjuan Yu, Bart van de Sluis, Jan van Deur

Fuente: http://plos.srce.hr/



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