Left ventricular dysfunction with reduced functional cardiac reserve in diabetic and non-diabetic LDL-receptor deficient apolipoprotein B100-only mice

Cardiovascular Diabetology

Original Investigation

Fatima Bosch¹  Seppo Ylä-Herttuala²  Petri I Mäkinen²  Elina Loponen²  Suvi E Heinonen²  Mari Merentie²  Ivana Kholová³  Markku Laakso⁴  Marja Hedman⁵ 

[1] Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, E-08193, Bellaterra, Spain;Department of Biotechnology and Molecular Medicine at A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland;Department of Biotechnology and Molecular Medicine at A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland;Pathology, Laboratory Centre, Tampere University Hospital, P.O. Box 2000, FI-33521, Tampere, Finland;Department of Medicine, University of Eastern Finland and Kuopio University Hospital, FI-70210, Kuopio, Finland;Heart Center, Kuopio University Hospital, P.O. Box 1777, FI-70211, Kuopio, Finland;

关键词: Myocardial Perfusion;    Left Coronary Artery;    Dobutamine Stress Echocardiography;    Aortic Sinus;    Cardiac Reserve;   

DOI  :  10.1186/1475-2840-10-59

 received in 2011-04-10, accepted in 2011-06-30,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundLack of suitable mouse models has hindered the studying of diabetic macrovascular complications. We examined the effects of type 2 diabetes on coronary artery disease and cardiac function in hypercholesterolemic low-density lipoprotein receptor-deficient apolipoprotein B100-only mice (LDLR-/-ApoB100/100).Methods and results18-month-old LDLR-/-ApoB100/100 (n = 12), diabetic LDLR-/-ApoB100/100 mice overexpressing insulin-like growth factor-II (IGF-II) in pancreatic beta cells (IGF-II/LDLR-/-ApoB100/100, n = 14) and age-matched C57Bl/6 mice (n = 15) were studied after three months of high-fat Western diet. Compared to LDLR-/-ApoB100/100 mice, diabetic IGF-II/LDLR-/-ApoB100/100 mice demonstrated more calcified atherosclerotic lesions in aorta. However, compensatory vascular enlargement was similar in both diabetic and non-diabetic mice with equal atherosclerosis (cross-sectional lesion area ~60%) and consequently the lumen area was preserved. In coronary arteries, both hypercholesterolemic models showed significant stenosis (~80%) despite positive remodeling. Echocardiography revealed severe left ventricular systolic dysfunction and anteroapical akinesia in both LDLR-/-ApoB100/100 and IGF-II/LDLR-/-ApoB100/100 mice. Myocardial scarring was not detected, cardiac reserve after dobutamine challenge was preserved and ultrasructural changes revealed ischemic yet viable myocardium, which together with coronary artery stenosis and slightly impaired myocardial perfusion suggest myocardial hibernation resulting from chronic hypoperfusion.ConclusionsLDLR-/-ApoB100/100 mice develop significant coronary atherosclerosis, severe left ventricular dysfunction with preserved but diminished cardiac reserve and signs of chronic myocardial hibernation. However, the cardiac outcome is not worsened by type 2 diabetes, despite more advanced aortic atherosclerosis in diabetic animals.

【 授权许可】

Unknown   
© Heinonen et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.