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




Left ventricular dysfunction with reduced functional cardiac reserve in diabetic and non-diabetic LDL-receptor deficient apolipoprotein B100-only mice - Download this document for free, or read online. Document in PDF available to download.

Cardiovascular Diabetology

, 10:59

First Online: 30 June 2011Received: 10 April 2011Accepted: 30 June 2011

Abstract

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 LDLRApoB.

Methods and results18-month-old LDLRApoB n = 12, diabetic LDLRApoB mice overexpressing insulin-like growth factor-II IGF-II in pancreatic beta cells IGF-II-LDLRApoB, n = 14 and age-matched C57Bl-6 mice n = 15 were studied after three months of high-fat Western diet. Compared to LDLRApoB mice, diabetic IGF-II-LDLRApoB 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 LDLRApoB and IGF-II-LDLRApoB 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.

ConclusionsLDLRApoB 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.

AbbreviationsAautophagosome

amabnormal mitochondria

ANOVAanalysis of variance

Apoapolipoprotein

AWanterior wall

CADcoronary artery disease

cfcollagen fibril

CPScontrast pulse sequence

ddiastole

dbdense bodies

EDend-diastole

EFejection fraction

EKVelectrocardiogram kilohertz-based visualization

ESend-systole

FSfractional shortening

gglycogen

GTTglucose tolerance test

IDinternal diameter

IGF-IIinsulin-like growth factor-II

llysosome

LAXlateral axis

LDLRlow density lipoprotein receptor

LVleft ventricle

mmyofiber

mfmyelin figures

MImyocardial infarction

nmnormal mitochondria

NDnot detected

PWposterior wall

ssystole

SAXsagittal axis

SDstandard deviation

SR-BIscavenger receptor class B type I

Volvolume.

Electronic supplementary materialThe online version of this article doi:10.1186-1475-2840-10-59 contains supplementary material, which is available to authorized users.

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Author: Suvi E Heinonen - Mari Merentie - Marja Hedman - Petri I Mäkinen - Elina Loponen - Ivana Kholová - Fatima Bosch - Markk

Source: https://link.springer.com/article/10.1186/1475-2840-10-59







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