[Development of new anti-atherosclerotic drugs based on the phenotypic modulation of vascular smooth muscle cells].
We have established a novel smooth muscle cell line (SVS) which retains the expression of specific markers for smooth muscle cells, such as smooth muscle myosin-1, calponin and SM22 alpha, from temperature-sensitive SV40 large T-antigen transgenic mice. SVS cells showed temperature-dependent growth and the expression of smooth muscle markers, showing that the differentiation stage can be controlled in this cell line by culture temperature. We have constructed luciferase-reporter cell lines for calponin and SM22 alpha genes by using SVS cells. We detected some compounds including ascorbic acid, which stimulated the expression of smooth muscle markers by the reporter assay. Ascorbic acid and its long lasting derivatives stimulated the expression of markers continuously. Moreover, ascorbic acid activated the expression of markers in synthetic SMCs seen in the intima of a rat balloon injury model. Thus, this reporter system should be useful for discovery of new antiatherosclerotic drugs.
Matsuda
Y
Y
Vessel Research Laboratory Co., Ltd., Tokyo, Japan.
Hasegawa
K
K
D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy*; D001205:Ascorbic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D002135:Calcium-Binding Proteins / Q000032:analysis; D002460:Cell Line; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000032:analysis; D009124:Muscle Proteins / Q000032:analysis; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects*; D009218:Myosins / Q000032:analysis; D000096985:Calponins
D001205:Ascorbic Acid; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D009218:Myosins; D000096985:Calponins; C058992:Tagln protein, mouse; C051615:transgelin