Aims: The aim of this study was to investigate the mechanisms by which nicotine increases vascular smooth muscle cell (VSMC) proliferation and post-injury neointimal formation.
Methods And Results: Vascular injury was inflicted in the right iliac artery of nicotine-treated and control rats. Nicotine increased post-injury VSMC proliferation (Ki67(+) cells) and neointimal formation (neointima/media ratio, 0.42 ± 0.23 vs. 0.14 ± 0.07, P= 0.02). To determine the mechanisms by which nicotine exacerbates VSMC proliferation, cultured cells were exposed to nicotine, and signalling pathways leading to cell proliferation were studied. Nicotine activated extracellular signal-regulated kinase (ERK) 1/2 in a dose- and time-dependent manner. The blockade of this signalling axis abolished nicotine-mediated proliferation. Functional nicotinic acetylcholine receptors and Ca(2+) influx were necessary for ERK1/2 activation and nicotine-induced mitogenesis in VSMCs. Downstream to ERK1/2, nicotine induced the phosphorylation of Ets-like gene 1 in a timely co-ordinated manner with the up-regulation of the atherogenic transcription factor, early growth response 1 (Egr-1). The treatment of balloon-injured arteries with a lentivirus vector carrying a short hairpin RNA against Egr-1 abolished the deleterious effect of nicotine on vascular remodelling.
Conclusion: Nicotine acts through its receptors in VSMC to activate the ERK-Egr-1 signaling cascade that induces cell proliferation and exacerbates post-injury neointimal development.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980942 | PMC |
| http://dx.doi.org/10.1093/cvr/cvq213 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Regulation of inflammatory responses: Harnessing the Ruan Mai Jian targeting of EphA2/ephrinA1 pathway to enhance atherosclerosis amelioration.
Phytomedicine
January 2025
Department of Geriatrics, Affiliated Longhua Hospital of Shanghai University of Traditional Chinese Medicine, 725 South Wanping Rd, Xuhui Area, Shanghai 200032, China. Electronic address:
Background: Atherosclerosis is a major contributor to global cardiovascular morbidity and mortality, driven by the chronic inflammatory proliferation of vascular smooth muscle cells (VSMCs), which destabilizes atherosclerotic plaques. The EphA2/ephrinA1 signaling pathway plays a critical role in modulating VSMC inflammatory responses, making it an attractive therapeutic target. However, the clinical application of EphA2 inhibitors remains limited due to safety concerns.
View Article and Find Full Text PDFExosome miR-199a-5p modulated vascular remodeling and inflammatory infiltration of Takayasu's arteritis.
Arthritis Res Ther
January 2025
Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Background: Advances in treatment have swiftly alleviated systemic inflammation of Takayasu's arteritis (TAK), while subclinical vascular inflammation and the ensuing arterial remodeling continue to present unresolved challenges in TAK. The phenotypic switching of vascular smooth muscle cells (VSMC) is regarded as the first step in vascular pathology and contributes to arterial remodeling. Exosomes facilitate the transfer and exchange of proteins and specific nucleic acids, thereby playing a significant role in intercellular communication.
View Article and Find Full Text PDFJOSD2 inhibits angiotensin II-induced vascular remodeling by deubiquitinating and stabilizing SMAD7.
Acta Pharmacol Sin
January 2025
Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, China.
Increased level of angiotensin II (Ang II) plays a central role in the development of hypertensive vascular remodeling. In this study, we identified the deubiquitinating enzyme Josephin domain-containing protein 2 (JOSD2) as a protective factor and investigated its molecular mechanism in Ang II-induced vascular remodeling. First, we found that JOSD2 was upregulated in aortic smooth muscle cells, but not in endothelial cells of Ang II-challenged mouse vascular tissues.
View Article and Find Full Text PDFDehydrocorydaline maintains the vascular smooth muscle cell contractile phenotype by upregulating Spta1.
Acta Pharmacol Sin
January 2025
The Fifth Affiliated Hospital, Guangdong Province & NMPA & State Key Laboratory, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
Vascular smooth muscle cell (VSMC) phenotypic switching plays a crucial role in the initiation and progression of atherosclerosis. Dehydrocorydaline (DHC), a major active component of the traditional Chinese herbal medicine Rhizoma Corydalis, exhibits diverse pharmacological effects. However, its impact on VSMCs remains largely unknown.
View Article and Find Full Text PDFThe senolytic cocktail, dasatinib and quercetin, impacts the chromatin structure of both young and senescent vascular smooth muscle cells.
Geroscience
January 2025
Laboratory of Molecular Basis of Aging, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-093, Warsaw, Poland.
One promising strategy to alleviate aging symptoms is the treatment with senolytics that is compounds which selectively eliminate senescent cells. Some therapies aim to reduce symptoms of cellular senescence without senescent cell eradication (senomorphic activity). However, senotherapies raise many questions concerning the selectivity, safety and efficiency of senolitic drugs.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!