Effect of Cholesterol on Sphingosylphosphorylcholine-Rho-kinase -mediated Cerebral Vasospasm

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Lipid rafts are cholesterol-enriched membrane microdomains that influence signal transduction. In this study, hypercholesterolemia increased vascular smooth muscle (VSM) cholesterol (but not PC, a major component of nonraft membranes) and sphingosylphosphorylcholine(SPC)-ROK-mediated VSM contraction. Depletion of VSM cholesterol (but not PC) byβ-cyclodextrin(β-CD) inhibited SPC-induced contraction. Treatment with β-CD decreased the mean % filipin III staining intensity of Human brain VSM cells. Depletion of VSM cholesterol by β -CD also decreased the raft marker ganglioside GM1 count per unit membrane length and inhibited SPC-induced contraction. These results indicate that cholesterol potentiates SPC-ROK-mediated contractions of importance in cerebral vasospasm and are compatible with a role for lipid rafts in this process.