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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cigarette smoking causes vascular endothelial dysfunction and is a major risk factor for cardiovascular diseases. Nicotine, a major constituent of cigarette smoke, has been shown to alter gene expression in endothelial cells; however, the regulatory pathways involved remain to be defined. We hypothesized that there might be distinct pathways that could be identified by systematic transcriptome analysis. Using the cDNA microarray approach, we ascertained the expression of over 4,000 genes in human coronary artery endothelial cells and identified a number of nicotine-modulated genes encoding a protein involving in signal transduction or transcriptional regulation. Among these were phosphatidylinositol phosphate kinase and diacylglycerol kinase, which are regulators of the inositol phospholipid pathway. Changes were also detected for transcription factors cAMP response element binding protein and nuclear factor-kappaB, of which the activities of both have been previously shown to be altered in nicotine-stimulated cells. The data from this study are relevant to understanding the mechanisms underlying the pathophysiological effect of nicotine and smoking, particularly on endothelial function and pathogenesis of atherosclerosis.
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PMID:Microarray analysis of nicotine-induced changes in gene expression in endothelial cells. 1132 64

Epidemiological studies have shown that cigarette smoking is a major cause of atherosclerosis. Oxidants as well as nicotine in cigarette smoke have been implicated in atherogenesis. To clarify the mechanism involved, we examined the chronic effects of nicotine and nicotine-free cigarette smoke extracts (CSE) on oxidative modification of low-density lipoprotein (LDL) in the plasma of Watanabe heritable hyperlipidemic rabbits and atherogenesis in the aorta. CSE was prepared by bubbling the gas phase of smoke (1 ml/three cigarettes) into phosphate buffer saline, and 3 ml of this CSE was injected daily into the ear vein of the rabbit for five months. The rabbits treated with CSE showed an increase in lipid peroxide levels, estimated as thiobarbituric acid reactive substances (TBARS), with a corresponding decrease in vitamin E levels in the plasma. They also showed enhanced oxidative modification of LDL, assessed by anion-exchange HPLC, incorporation into macrophages and measurement of TBARS. These events could be efficiently prevented by administering vitamin E (150 mg/kg/day, p.o.). Nicotine alone (0.5 mg/kg/day, s.c.) led to a temporary increase in the plasma triglyceride level. At the end of the experiment, CSE but not nicotine had caused progression of atherosclerotic lesions together with accumulation of cholesteryl ester in the thoracic aorta, while vitamin E had significantly prevented such atheromatous formation. These results indicate that oxidants in CSE can promote the development of atherosclerosis through oxidative modification of plasma LDL, particularly in hypercholesterolemia, and offer evidence for increased vitamin E utilization in smokers.
Atherosclerosis 2001 May
PMID:Oxidants in cigarette smoke extract modify low-density lipoprotein in the plasma and facilitate atherogenesis in the aorta of Watanabe heritable hyperlipidemic rabbits. 1136 3

We provide anatomic and functional evidence that nicotine induces angiogenesis. We also show that nicotine accelerates the growth of tumor and atheroma in association with increased neovascularization. Nicotine increased endothelial-cell growth and tube formation in vitro, and accelerated fibrovascular growth in vivo. In a mouse model of hind-limb ischemia, nicotine increased capillary and collateral growth, and enhanced tissue perfusion. In mouse models of lung cancer and atherosclerosis, we found that nicotine enhanced lesion growth in association with an increase in lesion vascularity. These effects of nicotine were mediated through nicotinic acetylcholine receptors at nicotine concentrations that are pathophysiologically relevant. The endothelial production of nitric oxide, prostacyclin and vascular endothelial growth factor might have a role in these effects.
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PMID:Nicotine stimulates angiogenesis and promotes tumor growth and atherosclerosis. 1143 37

On pharmacological and compositional grounds, cigarette mainstream smoke (MS) aerosol can be broadly categorized as consisting of the following constituents: carbon monoxide, other vapor phase components, particulate matter ('tar') and nicotine. The relative risk of coronary artery disease for smoking 20 cigarettes per day has been estimated by meta-analysis of five large prospective epidemiology studies to be 1.78. These four major smoke components are simultaneously delivered to the active smoker as a complex aerosol composed of several billion semi-liquid particles per cm(3) within the mixture of combustion gases. Fractional attribution of the 78% increase in reported risk to a given constituent is problematic because of the complex mixture. However, a significant literature exists which suggests that some general statements regarding smoke constituent-associated risks for development or exacerbation of myocardial infarction are supportable. First, the atherogenic potential of MS is associated with the particulate and vapor phases and not with CO. Nicotine might exert an indirect effect on atherosclerotic plaque development by increasing shear forces in main conduction arteries. Similarly, the thrombogenic potential is associated primarily with the particulate and vapor phases and also possibly with nicotine via platelet aggregation. Vasoconstriction probably results from the actions of nicotine and hypoxia from carbon monoxide. Finally, the arrhythmia-inducing potential may result from catecholamine release following nicotine exposure, with a questionable contribution from carbon monoxide.
Atherosclerosis 2001 Oct
PMID:Particulate and vapor phase constituents of cigarette mainstream smoke and risk of myocardial infarction. 1158 3

Although smoking is one of the major risk factors for the development of atherosclerosis, the exact mechanism of smoking-related vascular disease is not known. Smoking causes acute hemodynamic alterations such as increase in heart rate, systemic and coronary vascular resistance, myocardial contractility, and myocardial oxygen demand. These short-term effects could lower the ischemic threshold in smokers with coronary artery disease and contribute to the increased risk for acute cardiovascular events. Endothelial damage is thought to be an initiating event in atherosclerosis and early studies have demonstrated that long-term smoking has direct toxic effects with structural changes of human endothelial cells. Recent research has shown the importance of the functional role of the endothelium in regulating normal vascular tone, platelet-endothelial interactions, leukocyte adhesion and smooth muscle cell proliferation via synthesis and release of a variety of substances such as nitric oxide. There is strong evidence that smoking leads to endothelial dysfunction in both conductance and resistance vessels. This effect seems to be dose-related and reversible. The mechanism of endothelial dysfunction in smokers is not known, but increased degradation of nitric oxide by oxygen-derived free radicals has been suggested. In addition, smoking could cause oxidative inactivation of tetrahydrobiopterin, a critical cofactor of nitric oxide, leading to an uncoupling of the endothelial nitric oxide synthase with increased superoxide production and decreased nitric oxide bioactivity. Other pro-atherosclerotic effects of smoking are discussed. Given the enormous health hazard of tobacco use, complete abstinence from smoking should be achieved. Smoking cessation counseling should be given to healthy subjects and even more vigorously to patients with manifested disease. Every effort should be undertaken to prevent children and adolescents from starting to smoke. Brief tobacco dependence treatment is effective, and every tobacco user should be offered at least brief treatment at every office visit. More intensive treatment is more effective in producing long-term abstinence from tobacco. Nicotine replacement therapy (nicotine patches or gum), clinician-delivered social support, and skills training are the three most effective components of smoking cessation treatment.
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PMID:[Primary and secondary prevention of coronary heart disease: smoking]. 1243 60

Nicotine, the major immunomodulatory components of cigarette smoking, is among the leading risk factors in atherosclerosis and various other diseases. The subject of this study is to observe how nicotine affects the function of macrophages and vascular endothelial cells. The changes of nicotine on releasing of cytokines from Ana-1 were detected by radio-immunoassay (RIA) or enzyme-link immunosorbent assay (ELISA). The adhesion of monocytes to human umbilical vein endothelial cells (HUVECs) with Ana-1 supernatant-activated was evaluated through adhesion experiments. ELISA and RT-PCR methods examined expression of soluble adhesion molecular protein and their mRNA. Which cytokines in Ana-1 supernatant affecting HUVECs ability to express adhesion molecular were tested by adhesion blockade analysis and ELISA. The results showed TNF-alpha, IL-1beta could reach the peak with 0.06mM nicotine treated for 24 and 12 h on Ana-1, respectively, but IL-8 and IFN-gamma had no significant alter. Adhesion experiments proved treatment of HUVECs with supernatant of Ana-1 for 24 h obviously augmented the adhesion of monocytes to HUVECs. ELISA and PCR demonstrated expression of soluble intracellular adhesion molecule-1 protein (sICAM-1) increased sharply at 24 h, while soluble vascular cell adhesion molecule-1 protein (sVCAM-1) and soluble endothelial selectin protein (sE-selectin) rose at 9 h; ICAM-1, VCAM-1 and E-selectin mRNA had a similar tendency. Treatment of HUVECs with anti-TNF-alpha, anti-IL-1beta antibodies pre-neutralized supernatant of Ana-1 could block monocytes adhesion. In conclusion, our findings suggest that nicotine could augment macrophages releasing TNF-alpha and IL-1beta, furthermore TNF-alpha and IL-1beta could up-regulate the expression of adhesion molecule and increase adhesion of monocytes to HUVECs. These might be one of the reasons that leaded to endothelial dysfunction.
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PMID:Nicotine could augment adhesion molecule expression in human endothelial cells through macrophages secreting TNF-alpha, IL-1beta. 1545 19

Cigarette smoke, specifically the nicotine contained within, has been shown to cause ultrastructural changes in vascular endothelium resulting in the development of atherosclerosis. Our study examines the effects of nicotine on vascular smooth muscle cell (VSMC) migration and attempts to eludicidate the cellular mechanisms governing those effects. Bovine aortic VSMC were cultured in 10% fetal bovine serum (FBS) growth media and exposed to 10(-8) nicotine for varying periods of time. Boyden chamber chemotaxis assays and a scrape injury model using confluent cells were used to assess cell motility. Activation of the mitogen-activated protein kinases (MAPK), p38 and p44/42, was assessed using Western blotting methods. Nicotine, itself, did not cause significant VSMC migration. However, augmented migration was seen in nicotine-treated VSMCs (16.6+/-3-fold) and media (17.0+/-4-fold) with 10% FBS as chemoattractant. Inhibitors of p38 and p44/42 diminished this migration by 48.5+/-6% and 29.4+/-2%, respectively. Immunoblotting verified p38 and p44/42 activation with nicotine and inhibition with inhibitors of p38 and p44/42. Nicotine-treated endothelial cell (EC) conditioned media (CM) was shown to increase migration 20.3+/-l.l-fold. This chemotactic effect was diminished both with heat treatment and serial dilution. In conclusion, nicotine enhances the chemoatactiveness of VSMC. This migration is mediated via the MAPKs p38 and p44/42. Nicotine causes EC production of a chemoattractant molecule that enhances VSMC migration.
Atherosclerosis 2005 Feb
PMID:Nicotine induces mitogen-activated protein kinase dependent vascular smooth muscle cell migration. 1569 34

Nicotine, the addictive component of cigarette smoke, has been shown to have immunomodulatory effects. This drug alters proinflammatory cytokine production by immune cells, including lymphocytes, monocytes, and macrophages. The present study focuses on the effects of nicotine on infection by Chlamydia pneumoniae (Cpn), a ubiquitous intracellular pathogen which causes acute and chronic inflammatory diseases such as pulmonary infections, and may be associated with arthritis and atherosclerosis. Previous studies in our laboratory showed that lymphocytes and macrophages are susceptible to Cpn infection. The present study aimed at investigating the effect of nicotine on TGF-beta1, IL-10, IL-12, and TNF-alpha production in Cpn-infected human peripheral blood mononuclear cells (PBMCs). Cytokine levels in the supernatant were assessed by ELISA. The results showed that Cpn infection alters the expression levels of IL-10, IL-12, and TNF-alpha in a time-dependent fashion. Nicotine treatment of the Cpn-infected cells up-regulated IL-10, but not TNF-alpha and IL-12, and also resulted in significant down-regulation of TGF-beta1 production which was marked in the Cpn-infected control cells. The combined action of nicotine and Cpn on cytokine production may have an impact in chronic inflammatory diseases.
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PMID:Nicotine modulates cytokine production by Chlamydia pneumoniae infected human peripheral blood cells. 1571 Mar 43

Nicotine, a component of cigarette smoke, has been implicated in the pathogenesis of cardiovascular disease. We examined whether nicotine regulates angiotensin-converting enzyme (ACE), an enzyme that plays an important role in the pathophysiology of atherosclerosis and hypertension. Human umbilical cord vein endothelial cells were treated with nicotine (0.1-1 microM) alone or in combination with vascular endothelial growth factor (VEGF; 0.5 nM) or GF-109203X (GFX; 2.5 microM). The amount of ACE in intact endothelial cells was measured by an inhibitor-binding assay method, and ACE mRNA levels were quantified using LightCycler technology. Phosphorylated PKC levels were measured by Western immunoblotting. Nicotine did not modulate basal ACE production but significantly potentiated VEGF-induced ACE upregulation. Treatment of endothelial cells with the PKC inhibitor GFX totally blocked VEGF- and nicotine-induced ACE upregulation. VEGF induced PKC phosphorylation, which was potentiated by cotreatment with nicotine. We conclude that nicotine significantly potentiated VEGF-induced ACE upregulation. This effect was probably mediated by PKC phosphorylation. The interaction of nicotine with VEGF in ACE induction may contribute to the pathogenesis of smoking-related cardiovascular disease.
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PMID:Regulation of angiotensin-converting enzyme production by nicotine in human endothelial cells. 1596 16

Nicotine, a major toxic component of cigarette smoke, plays a key role in the development of cardiovascular disease and lung cancer. In the present study, we have synthesized an analog of curcumin and biomonitored its influence over biochemical marker enzymes and lipid profiles on nicotine-induced toxicity in Wistar rats. The effects were compared with that of curcumin, a well-known antioxidant and anti-hyperlipidemic agent. Toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg of body weight (5 days a week, for 22 weeks), and curcumin (80 mg/kg) was given simultaneously along with nicotine by intragastric intubation for 22 weeks. Measurements of activities of the biochemical marker enzymes aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase and of plasma lipid profiles were used to monitor the anti-hyperlipidemic effects of curcuminoids. In nicotine-treated rats, enhanced plasma marker enzymes and lipid profiles were observed. Administration of curcumin or curcumin analog to nicotine-treated rats significantly reduced the activity of marker enzymes and plasma lipid levels. Thus, our findings suggest that curcumin and its analog exert an anti-hyperlipidemic effect against nicotine-induced lung toxicity and may be a promising agent for treatment of hyperlipidemia and atherosclerosis.
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PMID:Modulatory effects of curcumin and curcumin analog on circulatory lipid profiles during nicotine-induced toxicity in Wistar rats. 1611 19


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