title: Effects of serotonin on expression of the LDL receptor family member LR11 and 7-ketocholesterol-induced apoptosis in human vascular smooth muscle cells.
abstract: Serotonin (5-HT) is a known mitogen for vascular smooth muscle cells (VSMCs). The dedifferentiation and proliferation/apoptosis of VSMCs in the arterial intima represent one of the atherosclerotic changes. LR11, a member of low-density lipoprotein receptor family, may contribute to the proliferation of VSMCs in neointimal hyperplasia. We conducted an in vitro study to investigate whether 5-HT is involved in LR11 expression in human VSMCs and apoptosis of VSMCs induced by 7-ketocholesterol (7KCHO), an oxysterol that destabilizes plaque. 5-HT enhanced the proliferation of VSMCs, and this effect was abolished by sarpogrelate, a selective 5-HT2A receptor antagonist. Sarpogrelate also inhibited the 5-HT-enhanced LR11 mRNA expression in VSMCs. Furthermore, 5-HT suppressed the 7KCHO-induced apoptosis of VSMCs via caspase-3/7-dependent pathway. These findings provide new insights on the changes in the differentiation stage of VSMCs mediated by 5-HT.
authors.affiliation: Center of Diabetes, Endocrinology and Metabolism, Toho University, Sakura Medical Center, 564-1, Shimoshizu, Sakura-City, Chiba 285-8741, Japan.
authors.forename: Daiji
authors.initials: D
authors.lastname: Nagayama
authors.affiliation: Center of Diabetes, Endocrinology and Metabolism, Toho University, Sakura Medical Center, 564-1, Shimoshizu, Sakura-City, Chiba 285-8741, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Ishihara
authors.affiliation: Department of Clinical Laboratory Medicine, Toho University, Sakura Medical Center, 564-1, Shimoshizu, Sakura-City, Chiba 285-8741, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Bujo
authors.affiliation: Department of Vascular Function, Toho University, Sakura Medical Center, 564-1, Shimoshizu, Sakura-City, Chiba 285-8741, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Shirai
authors.affiliation: Center of Diabetes, Endocrinology and Metabolism, Toho University, Sakura Medical Center, 564-1, Shimoshizu, Sakura-City, Chiba 285-8741, Japan. Electronic address: ichiro.tatsuno@med.toho-u.ac.jp.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tatsuno
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007653:Ketocholesterols / Q000494:pharmacology; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013386:Succinates / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D007653:Ketocholesterols; D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C102582:SORL1 protein, human; D012702:Serotonin Antagonists; D013386:Succinates; C064294:sarpogrelate; D012701:Serotonin; C003001:7-ketocholesterol
keywords: Apoptosis; LR11; Serotonin (5-HT); Vascular smooth muscle cells