Attenuation of isoproterenol-induced cardiac fibrosis in transgenic rats harboring an angiotensin-(1-7)-producing fusion protein in the heart
Open Access
- 5 January 2010
- journal article
- other
- Published by SAGE Publications in Therapeutic Advances in Cardiovascular Disease
- Vol. 4 (2), 83-96
- https://doi.org/10.1177/1753944709353426
Abstract
Objective: It has been shown that Ang-(1-7) has cardioprotective actions. To directly investigate the effects of Ang-(1-7) specifically in the heart, we generated and characterized transgenic (TG) rats which express an Ang-(1-7)-producing fusion protein driven by the α-MHC promoter. Methods and Results: After microinjection of the transgene into fertilized rat zygotes, we obtained four different transgenic lines. Homozygous animals were analyzed with regard to the expression profile of the transgene by ribonuclease protection assay. Transgene expression was detected mainly in the heart with weak or no expression in other organs. Heterozygous TG(hA-1-7)L7301 rats presented a significant increase in cardiac Ang-(1-7) concentration compared with control rats (17.1±2.1 versus 3.9±1.4 pg/mg protein in SD rats). Radiotelemetry analysis revealed that TG rats presented no significant changes in blood pressure and heart rate compared with normal rats. Overexpression of Ang-(1-7) in the heart produced slight improvement in resting cardiac function (+ dT/dt: 81530±1305.0 versus 77470±345.5 g/s bpm in SD rats, p < 0.05), which was in keeping with the enhanced [Ca2+] handling observed in cardiomyocytes of TG rats. TG(hA-1-7)L7301 rats also showed a greater capacity to withstand stress since TG rats showed a less pronounced deposition of collagen type III and fibronectin induced by isoproterenol treatment in the subendocardial area than in corresponding controls. In addition, hearts from TG rats showed reduced incidence and duration of reperfusion arrhythmias in comparison with SD rats. Conclusion: These results indicate that Ang-(1-7) has blood pressure-independent, antifibrotic effects, acting directly in the heart.Keywords
This publication has 33 references indexed in Scilit:
- Molecular Mechanisms Involved in the Angiotensin-(1-7)/Mas Signaling Pathway in CardiomyocytesHypertension, 2008
- Isoproterenol-induced impairment of heart function and remodeling are attenuated by the nonpeptide angiotensin-(1-7) analogue AVE 0991Life Sciences, 2007
- Beneficial versus harmful effects of Angiotensin (1-7) on impulse propagation and cardiac arrhythmias in the failing heartJournal of the Renin-Angiotensin-Aldosterone System, 2007
- ACE2 gene transfer attenuates hypertension-linked pathophysiological changes in the SHRPhysiological Genomics, 2006
- Angiotensin-(1–7) prevents development of severe hypertension and end-organ damage in spontaneously hypertensive rats treated with l-NAMEAmerican Journal of Physiology-Heart and Circulatory Physiology, 2006
- Evidence for a Functional Interaction of the Angiotensin-(1–7) Receptor Mas With AT 1 and AT 2 Receptors in the Mouse HeartHypertension, 2005
- Angiotensin (1-7) re-establishes impulse conduction in cardiac muscle during ischaemia-reperfusion. The role of the sodium pumpJournal of the Renin-Angiotensin-Aldosterone System, 2004
- What?s new in the renin-angiotensin system?Cellular and Molecular Life Sciences, 2004
- Plasma angiotensin(1–7) immunoreactivity is increased by salt load, water deprivation, and hemorrhagePeptides, 1994
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976