Left ventricular dysfunction with reduced functional cardiac reserve in diabetic and non-diabetic LDL-receptor deficient apolipoprotein B100-only mice
Heinonen, Suvi E. (AI Virtanen Institute for Molecular Sciences. University of Eastern Finland)
Merentie, Mari (AI Virtanen Institute for Molecular Sciences. University of Eastern Finland)
Hedman, Marja (Kuopio University Hospital ( Finlàndia))
Mäkinen, Petri I. (AI Virtanen Institute for Molecular Sciences. University of Eastern Finland)
Loponen, Elina (AI Virtanen Institute for Molecular Sciences. University of Eastern Finland)
Kholová, Ivana (AI Virtanen Institute for Molecular Sciences. University of Eastern Finland)
Bosch i Tubert, Fàtima (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Laakso, Markku (University of Eastern Finland and Kuopio University Hospital)
Ylä-Herttuala, Seppo (AI Virtanen Institute for Molecular Sciences. University of Eastern Finland)

Data:	2011
Resum:	Background: Lack 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 results: 18-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. Conclusions: LDLR-/-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.
Ajuts:	European Commission 115006
Nota:	Altres ajuts: Finnish Funding Agency for Technology and Innovation (70048/08)
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Cardiovascular diabetology, Vol. 10 (2011) , ISSN 1475-2840

DOI: 10.1186/1475-2840-10-59
PMID: 21718508

12 p, 6.8 MB

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