Key result
Selective HDL-raising human apo A-I gene transfer significantly reduced mortality (HR 0.42) and attenuated left ventricular dilatation after myocardial infarction in mice.
Why the study?
Does selective HDL-raising gene transfer improve survival and cardiac remodeling in mice post-myocardial infarction?
Does selective HDL-raising gene transfer improve survival and cardiac remodeling in mice post-myocardial infarction?
Hazard Ratio: 0.42 (95% CI 0.24–0.76)
p-value: p=<0.01
Selective HDL-raising gene transfer with human apo A-I significantly improves survival, attenuates infarct expansion, and preserves cardiac function after myocardial infarction in a mouse model.
Does not inform clinical practice; leaves open whether apo A-I gene transfer benefits extend beyond mice.
Post-myocardial infarction (MI) ejection fraction is decreased in patients with low high-density lipoprotein (HDL) cholesterol levels, independent of the degree of coronary atherosclerosis. The objective of this study is to evaluate whether selective HDL-raising gene transfer exerts cardioprotective effects post MI. Gene transfer in C57BL/6 low-density lipoprotein receptor (LDLr)(-/-) mice was performed with the E1E3E4-deleted adenoviral vector AdA-I, inducing hepatocyte-specific expression of human apo A-I, or with the control vector Adnull. A ligation of the left anterior descending coronary artery was performed 2 weeks after transfer or saline injection. HDL cholesterol levels were persistently 1.5-times (P<0.0001) higher in AdA-I mice compared with controls. Survival was increased (P<0.01) in AdA-I MI mice compared with control MI mice during the 28-day follow-up period (hazard ratio for mortality 0.42; 95% confidence interval 0.24-0.76). Longitudinal morphometric analysis demonstrated attenuated infarct expansion and inhibition of left ventricular (LV) dilatation in AdA-I MI mice compared with controls. AdA-I transfer exerted immunomodulatory effects and increased neovascularisation in the infarct zone. Increased HDL after AdA-I transfer significantly improved systolic and diastolic cardiac function post MI, and led to a preservation of peripheral blood pressure. In conclusion, selective HDL-raising gene transfer may impede the development of heart failure.
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Gordts et al. (2013) studied Myocardial infarction (n=93). AdA-I (human apo A-I gene transfer) vs. Adnull or saline was evaluated on Mortality (HR 0.42, 95% CI 0.24-0.76, p=<0.01). Selective HDL-raising human apo A-I gene transfer significantly reduced mortality (HR 0.42) and attenuated left ventricular dilatation after myocardial infarction in mice.
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