抄録
Hyperlipidemia is a major risk factor of cardiovascular events. We previously identified sphingosylphosphorylcholine (SPC) and Src family tyrosine kinase (Src-TK) as upstream mediators of the Rho-kinase (ROK)-mediated Ca2+ sensitization of vascular smooth muscle (VSM), which plays a pivotal role in abnormal VSM contraction such as vasospasm. In the present study, we examined the possible link between hyperlipidemia (or cholesterol) and the SPC/Src-TK/ROK-mediated Ca2+ sensitization. In VSM strips obtained from hyperlipidemic patients and rabbits, the extent of the SPC-induced Ca2+ sensitization correlated well with total serum cholesterol level and was diminished by either cholesterol-lowering therapy or in vitro selective depletion of cholesterol in VSM tissue by β-cyclodextrin (β-CD). Immunofluorescent study using cultured VSM cells under confocal microscope showed that SPC induced the translocations of fyn, a member of Src-TK, and ROK from cytosol to cell membrane, where they were colocalized with markers of membrane lipid rafts (a cholesterol-enriched membrane microdomain) such as caveolin-1 and cholera toxin subunit B. β-CD treatment markedly reduced the labeling of these raft markers and diminished the SPC-induced translocations of fyn and ROK from cytosol to membrane lipid rafts. These findings suggest that cholesterol and its enriched membrane lipid rafts may contribute to the SPC/Src-TK/ROK-mediated Ca2+ sensitization of VSM. [Jpn J Physiol 55 Suppl:S72 (2005)]
