title: Dyslipidaemia in type II diabetic mice does not aggravate contractile impairment but increases ventricular stiffness.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Laboratory of Experimental Cardiac Surgery, Department of Cardiovascular Disease, Katholieke Universiteit Leuven, Provisorium I, Minderbroedersstraat 19, K.U.Leuven postbus 01033 - FEHA, 3000 Leuven, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Van den Bergh
authors.forename: Annelies
authors.initials: A
authors.lastname: Vanderper
authors.forename: Peter
authors.initials: P
authors.lastname: Vangheluwe
authors.forename: Fanny
authors.initials: F
authors.lastname: Desjardins
authors.forename: Ines
authors.initials: I
authors.lastname: Nevelsteen
authors.forename: Wim
authors.initials: W
authors.lastname: Verreth
authors.forename: Frank
authors.initials: F
authors.lastname: Wuytack
authors.forename: Paul
authors.initials: P
authors.lastname: Holvoet
authors.forename: Willem
authors.initials: W
authors.lastname: Flameng
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Balligand
authors.forename: Paul
authors.initials: P
authors.lastname: Herijgers
mesh_terms: D000818:Animals; D001794:Blood Pressure; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D050171:Dyslipidemias / Q000150:complications / Q000503:physiopathology*; D005260:Female; D020738:Leptin / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology; D011973:Receptors, LDL / Q000502:physiology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000502:physiology; D016277:Ventricular Function, Left
chemical_list: D020738:Leptin; D011973:Receptors, LDL; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases