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Expression of an angiotensin-(1-7)-producing fusion protein produces cardioprotective effects in rats

Item Type:Article
Title:Expression of an angiotensin-(1-7)-producing fusion protein produces cardioprotective effects in rats
Creators Name:Santos, R.A.S. and Ferreira, A.J. and Nadu, A.P. and Braga, A.N.G. and de Almeida, A.P. and Campagnole-Santos, M.J. and Baltatu, O. and Iliescu, R. and Reudelhuber, T.L. and Bader, M.
Abstract:Angiotensin-(1-7) [ANG-(1-7)] is a recently described heptapeptide product of the renin-angiotensin system. Because biosynthesis of ANG-(1-7) increases in animals treated with cardioprotective drugs and inactivation of the gene for angiotensin converting enzyme 2 [an enzyme involved in the biosynthesis of ANG-(1-7)] leads to the development of cardiac dysfunction, it has been suggested that ANG-(1-7) has cardioprotective properties. To directly test this possibility, we have generated transgenic rats that chronically overproduce ANG-(1-7) by using a novel fusion protein methodology. TGR(A1-7)3292 rats show testicular-specific expression of a cytomegalovirus promoter-driven transgene, resulting in a doubling of circulating ANG-(1-7) compared with nontransgenic control rats. Radiotelemetry hemodynamic measurements showed that transgenic rats presented a small but significant increase in daily and nocturnal heart rate and a slight but significant increase in daily and nocturnal cardiac contractility estimated by dP/d t measurements. Strikingly, TGR(A1-7)3292 rats were significantly more resistant than control animals to induction of cardiac hypertrophy by isoproterenol. In addition, transgenic rats showed a reduced duration of reperfusion arrhythmias and an improved postischemic function in isolated Langendorff heart preparations. These results support a cardioprotective role for circulating ANG-(1-7) and provide a novel tool for evaluating the functional role of ANG-(1-7).
Keywords:Engineered Protein, Heart Hypertrophy, Renin-Angiotensin System, Animals, Rats
Source:Physiological Genomics
Publisher:American Physiological Society
Page Range:292-299
Date:1 January 2004
Official Publication:https://doi.org/10.1152/physiolgenomics.00227.2003
PubMed:View item in PubMed

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