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Identification of apolipoprotein D as a cardioprotective gene using a mouse model of lethal atherosclerotic coronary artery disease

2013; National Academy of Sciences; Volume: 110; Issue: 42 Linguagem: Inglês

10.1073/pnas.1315986110

1091-6490

Kosuke Tsukamoto, D.R. Mani, Jianru Shi, Songwen Zhang, Darrow E. Haagensen, Fumiyuki Otsuka, Jian Guan, Jonathan D. Smith, Wei Weng, Ronglih Liao, Frank D. Kolodgie, Renu Virmani, Monty Krieger,

Cardiac Fibrosis and Remodeling

Significance Coronary artery disease (CAD) is a major cause of death and disability. Genetically modified SR-BI/apoE double KO (dKO) mice spontaneously exhibit many features of human CAD, including hypercholesterolemia, clogged arteries, myocardial infarction (MI) (or heart attack), heart failure, and premature death. We identified many changes in gene expression in dKO hearts [e.g., increases in apolipoprotein D (apoD)] during CAD development and compared them to those occurring after surgically induced MI. Additional studies showed that apoD partially protected mice from experimentally induced MI (temporarily blocking a coronary artery) and partially protected isolated rat heart muscle cells from temporary oxygen deprivation. We conclude that dKO mice are useful models for human CAD and apoD may naturally help protect hearts from clogged arteries.