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Effects of transgenic endothelin‐2 overexpression on diabetic cardiomyopathy in rats
Author(s) -
Liefeldt L.,
Rylski B.,
Walcher F.,
Manhart J.,
Kron S.,
Rosenke Y.W.,
Paul M.,
Neumayer H.H.,
Amann K.,
Peters H.
Publication year - 2010
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2009.02251.x
Subject(s) - medicine , endocrinology , transgene , diabetic cardiomyopathy , endothelin receptor , streptozotocin , endothelin 1 , diabetes mellitus , muscle hypertrophy , genetically modified mouse , cardiomyopathy , type 2 diabetes , myocyte , biology , receptor , heart failure , gene , biochemistry
Eur J Clin Invest 2010; 40 (3): 203–210 Abstract Background Transgenic overexpression of human endothelin‐2 in rats was used to characterize the contribution of endothelin to diabetic cardiomyopathy. Materials and methods Diabetes mellitus was induced by streptozotocin in transgenic rats and transgene‐negative controls. Nondiabetic animals were included as well to form a 4‐group study design. Heart morphological and molecular alterations were analysed following 6 months of hyperglycaemia. Results Plasma endothelin concentrations were significantly higher in both transgenic groups than in wild‐type groups (nondiabetic: 3·5 ± 0·4 vs. 2·1 ± 0·2, P < 0·05; diabetic: 4·5 ± 0·4 vs. 2·5 ± 0·4 fmol mL −1 , P < 0·01). Diabetes induced cardiac hypertrophy in both wild‐type and transgenic rats and showed the highest myocardial interstitial tissue volume density in diabetic transgenic rats (1·5 ± 0·07%) as compared with nondiabetic transgenic (1·1 ± 0·03%), nondiabetic wild‐type (0·8 ± 0·01%) and diabetic wild‐type rats (1·1 ± 0·03%; P < 0·01 for all comparisons). A similar pattern with the most severe changes in the enothelin‐2 transgenic, diabetic animals was observed for hypertrophy of the large coronary arteries and the small intramyocardial arterioles respectively. Cardiac mRNA expression of endothelin‐1, endothelin receptors type A and B were altered in some degree by diabetes or transgenic overexpression of endothelin‐2, but not in a uniform manner. Blood pressure did not differ between any of the four groups. Conclusions Overexpression of the human endothelin‐2 gene in rats aggravates diabetic cardiomyopathy by more severe coronary and intramyocardial vessel hypertrophy and myocardial interstitial fibrosis. This transgenic intervention provides further and independent support for a detrimental, blood pressure‐independent role of endothelins in diabetic cardiac changes.