A novel trigger for cholesterol-dependent smooth muscle contraction mediated by the sphingosylphosphorylcholine-Rho-kinase pathway in the rat basilar artery: a mechanistic role for lipid rafts
| Autor: | Michiyasu Suzuki, Kazutaka Sugimoto, Masakatsu Tamechika, Masami Fujii, Fumiaki Oka, Yuji Owada, Sadahiro Nomura, Satoshi Shirao, Hirokazu Sadahiro, Hideyuki Ishihara, Hiroyasu Koizumi, Yoshiteru Kagawa, Hiroshi Yoneda, Mizuya Shinoyama |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Vascular smooth muscle Contraction (grammar) Pyridines Phosphorylcholine Biology Muscle Smooth Vascular Rats Sprague-Dawley chemistry.chemical_compound Membrane Microdomains Sphingosine Internal medicine medicine Animals Vasospasm Intracranial Lipid raft Rho-associated protein kinase Antihypertensive Agents rho-Associated Kinases Cholesterol beta-Cyclodextrins Membrane Proteins Vasospasm Smooth muscle contraction medicine.disease Amides Dietary Fats Rats Endocrinology Neurology chemistry Basilar Artery cardiovascular system lipids (amino acids peptides and proteins) Original Article Neurology (clinical) medicine.symptom Cardiology and Cardiovascular Medicine Carotid Artery Internal Muscle contraction Muscle Contraction Signal Transduction |
| Zdroj: | Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 35(5) |
| ISSN: | 1559-7016 |
| Popis: | Hyperlipidemia is a risk factor for abnormal cerebrovascular events. Rafts are cholesterol-enriched membrane microdomains that influence signal transduction. We previously showed that Rho-kinase-mediated Ca2+ sensitization of vascular smooth muscle (VSM) induced by sphingosylphosphorylcholine (SPC) has a pivotal role in cerebral vasospasm. The goals of the study were to show SPC-Rho-kinase-mediated VSM contraction in vivo and to link this effect to cholesterol and rafts. The SPC-induced VSM contraction measured using a cranial window model was reversed by Y-27632, a Rho-kinase inhibitor, in rats fed a control diet. The extent of SPC-induced contraction correlated with serum total cholesterol. Total cholesterol levels in the internal carotid artery (ICA) were significantly higher in rats fed a cholesterol diet compared with a control diet or a β-cyclodextrin diet, which depletes VSM cholesterol. Western blotting and real-time PCR revealed increases in flotillin-1, a raft marker, and flotillin-1 mRNA in the ICA in rats fed a cholesterol diet, but not in rats fed the β-cyclodextrin diet. Depletion of cholesterol decreased rafts in VSM cells, and prevention of an increase in cholesterol by β-cyclodextrin inhibited SPC-induced contraction in a cranial window model. These results indicate that cholesterol potentiates SPC-Rho-kinase-mediated contractions of importance in cerebral vasospasm and are compatible with a role for rafts in this process. |
| Databáze: | OpenAIRE |
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