title: L-ascorbic acid stimulates expression of smooth muscle-specific markers in smooth muscle cells both in vitro and in vivo.
abstract: The dedifferentiation of vascular smooth muscle cells (VSMCs) plays a critical role in the progression of atherosclerosis and restenosis after angioplasty. Thus, factors that stimulate smooth muscle cell differentiation should be useful for therapy for these diseases. Previously, we found that l-ascorbic acid (L-Asc) induces the expression of smooth muscle-specific genes in a pluripotent bone marrow stromal cell line, TBR-B. This finding suggests that l-Asc stimulates the differentiation of smooth muscle cells. In the present study, we investigated the effects of l-Asc and its derivatives on the differentiation state of VSMCs in vitro and in vivo. l-Asc and its long-lasting derivatives stimulated the production of smooth muscle-specific myosin heavy chain-1 (SM1) and calponin 1 in a dose-dependent manner in rat cultured VSMCs, and the elevated production of SM1 and calponin 1 was maintained for at least 2 weeks. Moreover, oral administration of 3 g/kg of l-Asc to the balloon-injured rats induced a higher expression of SM1 and calponin 1 in the injured arteries compared with that from administration of the delivery vehicle alone. These data demonstrated new biologic activity, such as the stimulation of VSMC differentiation, of l-Asc and its long-lasting derivatives. In addition, these compounds may serve as useful tools for analysis of the differentiation of VSMCs and for therapy for vascular diseases.
authors.affiliation: Vessel Research Laboratory Co., Ltd., Asahimachi, Machida, Tokyo, Japan. emi.arakawa@kyowa.co.jp
authors.forename: Emi
authors.initials: E
authors.lastname: Arakawa
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Junko
authors.initials: J
authors.lastname: Irie
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ide
authors.forename: Junko
authors.initials: J
authors.lastname: Ushiki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Shoji
authors.initials: S
authors.lastname: Oda
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D008297:Male; D008840:Microfilament Proteins; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D000096985:Calponins
chemical_list: D000975:Antioxidants; D001205:Ascorbic Acid; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D018995:Myosin Heavy Chains; D000096985:Calponins