Protection Against Ischemia/Reperfusion Injury by High-Density Lipoprotein and Its Components

Abstract

Identification of Apolipoprotein D as a Cardioprotective Gene Using a Mouse Model of Lethal Atherosclerotic Coronary Artery Disease Tsukamoto et al Proc Natl Acad Sci U S A . 2013;110:17023–17028. Apolipoprotein D is expressed in many tissues after injury, such as reperfusion injury after myocardial infarction. Antioxidant activity of apolipoprotein D appears to confer cardioprotective properties after myocardial infarction in a mouse model of severe rapidly progressing coronary atherosclerosis and in a mouse model of ischemia/reperfusion injury. Mice with homozygous-null mutations in the high-density lipoprotein (HDL) scavenger receptor class B type I (SR-BI) and also with homozygous-null mutations in apolipoprotein E (apoE) experience development of severe occlusive coronary atherosclerosis and have myocardial infarction (MI) starting at approximately 31 days after birth. By 42 days after birth, ≈50% have died from cardiac causes. Tsukamoto et al1 studied myocardial gene expression before MI (21 days after birth) and at 31 and 43 days after birth in these mice (SR-BI−/−/apoE−/−). The expression of the gene for osteopontin increased 416-fold, and the gene for apoD increased 80-fold. Because it had previously been reported that the gene for osteopontin increased post-MI,2–5 the authors concentrated on the study of apoD. In an ischemia/reperfusion injury model, adenoviral expression of apoD in the liver was associated with high plasma apoD levels and reduced MI size. In contrast, deficiency of apoD (in apoD-null mice) was associated with increased MI size. The ability of apoD to protect cultured rat cardiomyocytes from hypoxia/reoxygenation injury correlated with the ability of apoD to inhibit oxidation in an in vitro antioxidant assay, suggesting that the antioxidant properties of apoD are important in mediating its cardioprotective properties. The authors determined the time course …