{
   "source_x": "PMC",
   "title": "Identification of apolipoprotein D as a cardioprotective gene using a mouse model of lethal atherosclerotic coronary artery disease",
   "doi": "http://dx.doi.org/10.1073/pnas.1315986110",
   "pmcid": "PMC3801016",
   "abstract": "Mice with homozygous null mutations in the HDL receptor (scavenger receptor class B, type I, or SR-BI) and apolipoprotein E (apoE) genes [SR-BI/apoE double KO (SR-BI(\u2212/\u2212)/apoE(\u2212/\u2212) or dKO) mice] spontaneously develop occlusive, atherosclerotic coronary artery disease (CAD) and die prematurely (50% mortality at 42 d of age). Using microarray mRNA expression profiling, we identified genes whose expression in the hearts of dKO mice changed substantially during disease progression [at 21 d of age (no CAD), 31 d of age (small myocardial infarctions), and 43 d of age (extensive myocardial infarctions) vs. CAD-free SR-BI(+/\u2212)/apoE(\u2212/\u2212) controls]. Expression of most genes that increased >sixfold in dKO hearts at 43 d also increased after coronary artery ligation. We examined the influence and potential mechanism of action of apolipoprotein D (apoD) whose expression in dKO hearts increased 80-fold by 43 d. Analysis of ischemia/reperfusion-induced myocardial infarction in both apoD KO mice and wild-type mice with abnormally high plasma levels of apoD (adenovirus-mediated hepatic overexpression) established that apoD reduces myocardial infarction. There was a correlation of apoD\u2019s ability to protect primary cultured rat cardiomyocytes from hypoxia/reoxygenation injury with its potent ability to inhibit oxidation in a standard antioxidation assay in vitro. We conclude that dKO mice represent a useful mouse model of CAD and apoD may be part of an intrinsic cardioprotective system, possibly as a consequence of its antioxidation activity.",
   "authors": [
      "['Tsukamoto, Kosuke', 'Mani, D. R.', 'Shi, Jianru', 'Zhang, Songwen', 'Haagensen, Darrow E.', 'Otsuka, Fumiyuki', 'Guan, Jian', 'Smith, Jonathan D.', 'Weng, Wei', 'Liao, Ronglih', 'Kolodgie, Frank D.', 'Virmani, Renu', 'Krieger, Monty']"
   ],
   "id": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3801016"
}