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International Journal of Hypertension (1)
Journal of Biomedicine and Biotechnology (1)
Roks, Anton J. M. (2)
Danser, A. H. Jan (1)
Durik, Matej (1)
Goris, Maaike (1)
Groenewegen, Hendrik C. (1)
Haas Jimoh Akanbi, Marijke (1)
Hillebrands, Jan-Luuk (1)
Klatter, Flip A. (1)
Kuipers, Anneke (1)
Moll, Gert (1)
Onuta, Geanina (1)
Rink, Rick (1)
Rozing, Jan (1)
Walther Boer, Mark (1)
de Smet, Bart J. G. L. (1)
van Goor, Harry (1)
van Veghel, Richard (1)
Year of Publication
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
van Veghel, Richard
Haas Jimoh Akanbi, Marijke
Danser, A. H. Jan
International Journal of Hypertension
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.
Long-Term Type 1 Diabetes Enhances In-Stent Restenosis after Aortic Stenting in Diabetes-Prone BB Rats
Groenewegen, Hendrik C.
Klatter, Flip A.
Walther Boer, Mark
van Goor, Harry
de Smet, Bart J. G. L.
Journal of Biomedicine and Biotechnology
Type 1 diabetic patients have increased risk of developing in-stent restenosis following endovascular stenting. Underlying pathogenetic mechanisms are not fully understood partly due to the lack of a relevant animal model to study the effect(s) of long-term autoimmune diabetes on development of in-stent restenosis. We here describe the development of in-stent restenosis in long-term (~7 months) spontaneously diabetic and age-matched, thymectomized, nondiabetic Diabetes Prone BioBreeding (BBDP) rats (n = 6-7 in each group). Diabetes was suboptimally treated with insulin and was characterized by significant hyperglycaemia, polyuria, proteinuria, and increased HbA1c levels. Stented abdominal aortas were harvested 28 days after stenting. Computerized morphometric analysis revealed significantly increased neointima formation in long-term diabetic rats compared with nondiabetic controls. In conclusion, long-term autoimmune diabetes in BBDP rats enhances in-stent restenosis. This model can be used to study the underlying pathogenetic mechanisms of diabetes-enhanced in-stent restenosis as well as to test new therapeutic modalities.
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