Abstract 1131: Overexpression of Apolipoprotein-B Improves Cardiac Function and Increases Survival in Mice with Myocardial Infarction
Accumulation of intracellular lipids during myocardial infarction (MI) and heart failure (HF) causes cell dysfunction and cell death. Endogenous production of myocardial apoB particles may isolate and export superfluous and toxic intracellular lipids. The aims of this study were:
to investigate whether cardiac apoB is activated during MI and CHF, and,
to investigate the effects of apolipoprotein-B (apoB) overexpression on myocardial function and survival after MI.
Ischemia-reperfusion injury (IR), MI and HF were induced by by temporary or permanent ligation of the left coronary artery in the transgenic mice with overexpression of apoB (n=27; ~ 60 % more myocardial apoB) and the wild- type controls (n=40). Myocardial apoB content was analysed by standard binding assay at different time points after MI and developing HF. Echocardiography was performed under resting and stress (dobutamine) conditions at baseline (before MI) and 2, 4 and 6 weeks postinfarction. Qualitative and quantitative analysis of myocardial lipids was performed by HPLC.
Post-MI survival rate was ~ 60 % higher in the ApoB transgenic mice (p < 0.05) compared to the controls. This was associated with improved systolic function (p < 0.05) and lower left ventricular volumes (p < 0.05). Myocardial production of apoB in the wild-type mice increased 2-fold (p < 0.05) at 6, 24 and 48 hours after IR both in the injured and the remote myocardium compared to the non-infarcted controls. However, 8 weeks post-MI, myocardial apoB decreased markedly to 20 % of the controls (p < 0.05).
Cardiac overexpression of apoB increases survival and improves myocardial function post-MI. While myocardial apoB production is increased during acute and subacute post-MI phase, it decreases over the time to the subnormal levels. Myocardial apoB system may be important cardioprotective system involved in the maintenance of normal cardiac function, morphology and metabolism.