The Effect of the Thioether-Bridged, Stabilized Angiotensin-(1–7) Analogue Cyclic Ang-(1–7) on Cardiac Remodeling and Endothelial Function in Rats with Myocardial Infarction

Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
International journal of hypertension 01/2012; 2012:536426. DOI: 10.1155/2012/536426
Source: PubMed


Modulation of renin-angiotensin system (RAS) by angiotensin-(1–7) (Ang-(1–7)) is an attractive approach to combat the detrimental consequences of myocardial infarction (MI). However Ang-(1–7) has limited clinical potential due to its unfavorable pharmacokinetic profile. We investigated effects of a stabilized, thioether-bridged analogue of Ang-(1–7) called cyclic Ang-(1–7) in rat model of myocardial infarction. Rats underwent coronary ligation or sham surgery. Two weeks thereafter infusion with 0.24 or 2.4 μg/kg/h cAng-(1–7) or saline was started for 8 weeks. Thereafter, cardiac morphometric and hemodynamic variables as wells as aortic endothelial function were measured.
The average infarct size was 13.8% and was not changed by cAng-(1–7) treatment. MI increased heart weight and myocyte size, which was restored by cAng-(1–7) to sham levels. In addition, cAng-(1–7) lowered left ventricular end-diastolic pressure and improved endothelial function. The results suggest that cAng-(1–7) is a promising new agent in treatment of myocardial infarction and warrant further research.

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    • "These positions have been shown to tolerate mutations in angiotensin-peptides without affecting their biological activity[31,32]. For example Asp1 and Pro7 have been replaced by glutamine and cysteine without negatively affecting the biological activity of the corresponding angiotensin-derived peptides[31,32]. The AT1-7 derived peptide was grafted into the cyclotide backbone between residues Gly1 and Ser32 using the β-amino and γ-carboxylic groups through the creation of two isopeptide bonds (Figure 1). "
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    • "Evidences have showed that angiotensin (Ang) II induces inflammation, leading to cardiac remodeling (Savoia and Volpe, 2011; Jia et al., 2012). On the other hand, the thioether-bridged, stabilized angiotensin-(1–7) analog cyclic ang-(1–7) exerts beneficial effect on the cardiac remodeling and endothelial function in rats with myocardial infarction (Capettini et al., 2012; Durik et al., 2012). The Ang II is a key effector peptide of the rennin-angiotensin system in regulating blood pressure, homeostasis, and cell proliferation. "
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