title: Low-dose Exogenous Ouabain Alleviates Cardiac Lipotoxicity Through Suppressing Expression of CD36.
abstract: CD36 is a key transporter involved in fatty acid (FA) uptake and contributes to the accumulation of FA in cardiomyocytes. The objective of this study was to investigate the role of ouabain, a glycoside regulator of Na(+)/K(+)-ATPase, in the regulation of CD36 expression and FA accumulation. FATP1 transgenic (Tg) mice with lipotoxic cardiomyopathy displayed significantly increased cardiac CD36 expression and free fatty acid accumulation. The data on enzyme-linked immunosorbent assay showed that endogenous ouabain was decreased in the serum of Tg mice versus wild-type mice. CD36 expression and free fatty acid accumulation in their primary cardiomyocytes were abated by treatment with 0.15-0.30 μM ouabain. CD36 expression was suppressed by 0.2 μM ouabain treatment, and the suppression was rescued by C-reactive protein. CD36 expression and free fatty acid accumulation in the heart were markedly reduced in Tg mice injected with 30 or 40 ng of ouabain (P < 0.01). Obvious fatty infiltration was found in noninjected Tg mice but not in the mice injected with 40 ng of ouabain. In conclusion, low-dose exogenous ouabain increased Na(+)/K(+)-ATPase activity, suppressed C-reactive protein-mediated CD36 expression, and alleviated murine cardiac lipotoxicity in vitro and in vivo.
authors: Department of Cardiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors: Ning
authors: N
authors: Guo
authors: Wenting
authors: W
authors: Ai
authors: Xin
authors: X
authors: Jiang
authors: Yanping
authors: Y
authors: Ren
authors: Gang
authors: G
authors: Tian
authors: Xiaolin
authors: X
authors: Xue
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000096:biosynthesis*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005230:Fatty Acids, Nonesterified / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000633:toxicity*; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D010042:Ouabain / Q000008:administration & dosage*
chemical_list: D018955:CD36 Antigens; D005230:Fatty Acids, Nonesterified; D010042:Ouabain