Search resultsAlcohol inhibits smooth muscle cell proliferation via regulation of the notch signaling pathway
Title
Alcohol inhibits smooth muscle cell proliferation via regulation of the notch signaling pathway
Publication type
Journal Article
Year of Publication
2010
Authors
Journal
Arteriosclerosis, Thrombosis, and Vascular Biology
Volume
30
Issue
12
Pagination
2597 - 2603
Date published
2010
ISBN
10795642 (ISSN)
Keywords
alcohol, animal experiment, animal model, Animals, arterial wall thickness, article, athersclerosis, Basic Helix-Loop-Helix Transcription Factors, Carotid Arteries, carotid artery, Carotid Artery Diseases, Cell Cycle Proteins, cell proliferation, Cells, Cultured, controlled study, Coronary Vessels, Disease Models, Animal, Dose-Response Relationship, Drug, Ethanol, gene expression regulation, heart protection, human, human cell, Humans, Immunoglobulin J Recombination Signal Sequence-Binding Protein, intimal-medial thickening, Mice, Mice, Inbred C57BL, mouse, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, nonhuman, Notch, Notch1 receptor, priority journal, promoter region, Promoter Regions, Genetic, protein domain, Receptor, Notch1, restenosis, RNA Interference, RNA, Messenger, signal transduction, SMC growth, smooth muscle fiber, Time Factors, Transfection, vascular remodeling
Abstract
Objective- To determine the role of Notch signaling in mediating alcohol's inhibition of smooth muscle cell (SMC) proliferation. Methods and Results- Treatment of human coronary artery SMCs with ethanol (EtOH) decreased Notch 1 mRNA and Notch 1 intracellular domain protein levels, in the absence of any effect on Notch 3. EtOH treatment also decreased C-promoter binding factor-1 (CBF-1)/recombination signal-binding protein (RBP)-jk promoter activity and Notch target gene (hairy related transcription factor [HRT-1] or HRT-2) expression. These effects were concomitant with an inhibitory effect of EtOH on SMC proliferation. Overexpression of constitutively active Notch 1 intracellular domain or human hairy related transcription factor-1 (hHRT-1) prevented the EtOH-induced inhibition of SMC proliferation. In vivo, Notch 1 and HRT-1 mRNA expression was increased after ligation-induced carotid artery remodeling. The vessel remodeling response was inhibited in mice that received "moderate" amounts of alcohol by gavage daily; intimal-medial thickening was markedly reduced, and medial and neointimal SMC proliferating cell nuclear antigen expression was decreased. Moreover, Notch 1 and HRT-1 expression, induced after ligation injury, was inhibited by moderate alcohol consumption. Conclusion- EtOH inhibits Notch signaling and, subsequently, SMC proliferation, in vitro and in vivo. The modulation of Notch signaling in SMCs by EtOH may be relevant to the cardiovascular protective effects of moderate alcohol consumption purported by epidemiological studies.