Title: Dyslipidaemia in type II diabetic mice does not aggravate contractile impairment but increases ventricular stiffness
Authors: Van den Bergh, An
Vanderper, Annelies
Vangheluwe, Peter
Desjardins, Fanny
Nevelsteen, Ines
Verreth, Wim
Wuytack, Frank
Holvoet, Paul
Flameng, Willem
Balligand, Jean-Luc
Herijgers, Paul # ×
Issue Date: Jan-2008
Publisher: British Medical Association
Series Title: Cardiovascular Research vol:77 issue:2 pages:371-379
Abstract: AIMS: Type II diabetes, often associated with abdominal obesity, frequently leads to heart failure. Clinical and epidemiological evidence suggests that supplemental dyslipidaemia and hypertension, as clustered in the metabolic syndrome, aggravate the cardiovascular outcome. The differential impact of type II diabetes and the metabolic syndrome on left ventricular function, however, remains incompletely defined. METHODS AND RESULTS: We studied left ventricular function in vivo using pressure-volume analysis in obese diabetic mice with leptin deficiency (ob/ob) and obese diabetic dyslipidemic mice with combined leptin and low-density lipoprotein-receptor deficiency (DKO). ob/ob and DKO mice developed a diabetic cardiomyopathy, characterized by impaired contractility and relaxation, from the age of 24 weeks onwards. This was-at least partially-explained by increased apoptosis and disturbed Ca(2+) reuptake in the sarcoplasmic reticulum (SR) in both mouse models. DKO, but not ob/ob, developed increased end-diastolic ventricular stiffness, paralleled by increased left ventricular myocardial fibrosis. Cardiac output was preserved in ob/ob mice by favourable loading conditions, whereas it decreased in DKO mice. CONCLUSIONS: Type II diabetes in mice leads to impaired contractility and relaxation due to disturbed Ca(2+) reuptake in the SR, but only when dyslipidaemia and hypertension are superimposed does vascular-ventricular stiffening increase and left ventricular myocardial fibrosis develop.
ISSN: 0008-6363
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Atherosclerosis and Metabolism (-)
Experimental Cardiac Surgery (-)
Physiology Section (-)
Laboratory of Cellular Transport Systems
× corresponding author
# (joint) last author

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