Effects of serotonin on expression of the LDL receptor family member LR11 and 7-ketocholesterol-induced apoptosis in human vascular smooth muscle cells

• Published in: Biochemical and Biophysical Research Communications Vol. 446; no. 4; pp. 906 - 910
• Main Authors: Nagayama, Daiji, Ishihara, Noriko, Bujo, Hideaki, Shirai, Kohji, Tatsuno, Ichiro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.04.2014; Elsevier BV
• Subjects: 60 APPLIED LIFE SCIENCES; antagonists; APOPTOSIS; Apoptosis - drug effects; ARTERIOSCLEROSIS; CELL PROLIFERATION; Cell Proliferation - drug effects; Cells, Cultured; Enzyme Inhibitors; Enzyme Inhibitors - pharmacology; gene expression; HUMAN POPULATIONS; Humans; hyperplasia; IN VITRO; in vitro studies; Ketocholesterols; Ketocholesterols - pharmacology; LDL-Receptor Related Proteins; LDL-Receptor Related Proteins - genetics; LIPOPROTEINS; low density lipoprotein; LR11; Membrane Transport Proteins; Membrane Transport Proteins - genetics; MESSENGER-RNA; Muscle, Smooth, Vascular; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; MUSCLES; myocytes; Myocytes, Smooth Muscle; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; RECEPTORS; RNA, Messenger; RNA, Messenger - genetics; SEROTONIN; Serotonin (5-HT); Serotonin - metabolism; Serotonin Antagonists; Serotonin Antagonists - pharmacology; smooth muscle; Succinates; Succinates - pharmacology; Up-Regulation; Up-Regulation - drug effects; Vascular smooth muscle cells; LR11; Serotonin (5-HT); Vascular smooth muscle cells; Apoptosis
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2014.03.031

•The dedifferentiation of VSMCs in arterial intima is involved in atherosclerosis.•5-HT showed proliferative effect on VSMCs which was abolished by sarpogrelate.•5-HT enhanced expression of LR11 mRNA in VSMCs which was abolished by sarpogrelate.•5-HT suppressed 7KCHO-induced apoptosis of VSMCs via caspase-3/7-dependent pathway.•The mechanisms explain the 5-HT-induced remodeling of arterial structure. 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.