title: Cholesterol induces cardiac hypertrophy by activating the AKT pathway.
abstract: Cardiac hypertrophy leads to decompensated heart function, predisposition to heart failure, and sudden death due to physiological and pathological stimuli. Although high cholesterol is considered a principal risk factor for atherosclerosis and heart disease, it has not been shown whether cholesterol itself is sufficient to cause cardiac hypertrophy. In this study, we investigated whether cholesterol induces cardiac hypertrophy, and identified cellular mechanisms underlying hypertrophic responses using H9c2 cells as a model system. Here we show that cholesterol loading significantly increased the cellular surface area and upregulated hypertrophy marker gene, β-myosin-heavy chain (β-MHC). Cholesterol loading alone activated the extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)/AKT pathways. Conversely, cholesterol induced hypertrophic characteristic features such as increase in cellular surface area, and the expression of β-MHC mRNA is markedly inhibited by LY294002, a PI3K kinase inhibitor. These results suggest that cholesterol may play a key role in the development of cardiac hypertrophy through the activation of the PI3K/AKT pathway activation.
authors.affiliation: Molecular Recognition Research Center, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea; Department of Life & Pharmaceutical Sciences Ewha Womans University, Daehyun-dong, Seodaemun-gu, Seoul 120-750, Republic of Korea.
authors.forename: Hyunjung
authors.initials: H
authors.lastname: Lee
authors.forename: Young Sook
authors.initials: YS
authors.lastname: Yoo
authors.forename: Daekee
authors.initials: D
authors.lastname: Lee
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Song
mesh_terms: D015153:Blotting, Western; D006332:Cardiomegaly / Q000139:chemically induced* / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000494:pharmacology*; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002784:Cholesterol; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; Cardiac hypertrophy; Cholesterol; ERK; G-protein-coupled receptor; GPCR; GSK3β; H9c2 cells; IGF; MAPK; PI3K; extracellular signal-regulated kinase; insulin growth factor; mTOR; mammalian target of rapamycin; mitogen-activated protein kinase; phosphatidylinositol-3-kinase; phospho-glycogen synthase kinase-3β