Marked Impairment of Protease-Activated Receptor Type 1-Mediated Vasodilation and Fibrinolysis in Cigarette Smokers

Lang, Ninian N.; Guðmundsdóttir, Ingibjörg; Boon, Nicholas A.; Ludlam, Christopher A.; Fox, Keith A.A.; Newby, David E.

doi:10.1016/j.jacc.2008.04.003

Cited by 23 publications

(22 citation statements)

References 26 publications

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“…Increased t-PA would suggest an enhanced ability for fibrinolysis, but a rapid release of t-PA from the vascular endothelium is essential for an effective fibrinolysis. Studies could show that the t-PA release from the vascular bed was impaired in smokers (Lang et al 2008;Newby et al 1999;Takashima et al 2007) suggesting an impaired capacity of the endothelium to release t-PA acutely, despite high baseline concentrations of t-PA.…”

Section: Discussionmentioning

confidence: 99%

Plasma Fibrinolysis Parameters in Smokers and Non-smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study

Delgado

Siekmeier

Krämer

et al. 2015

Advances in Experimental Medicine and Biology

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Cardiovascular diseases (CVD) are an important cause of morbidity and mortality worldwide. Parameters of coagulation and fibrinolysis are risk factors of CVD and might be affected by cigarette smoking. Aim of our study was to analyze the effect of cigarette smoking on parameters of fibrinolysis in active smokers (AS) and life-time non-smokers (NS) of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study as well as the use of these parameters for risk prediction. We determined plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator antigen (t-PA), protein C activity, and D-dimers in 3,316 LURIC patients. Smoking status was assessed by a questionnaire and measurement of plasma cotinine concentration. Cox regression was used to assess the effect of parameters on mortality. We found that of the 3,316 LURIC patients 777 were AS and 1,178 NS. Within the observation period of 10 years (median) 221 AS and 302 NS died. In male AS vs. NS, PAI-1 (19.0 (10.0-35.0) vs. 15.0 (9.0-29.0) U/ml; p=0.026) and t-PA antigen (12.7 (9.6-16.3) vs. 11.6 (8.9-14.6) μg/l; p=0.020) were slightly increased, while t-PA activity was slightly decreased (0.63 (0.30-1.05) vs. 0.68 (0.42-1.10) U/l; p=0.005). In female AS vs. NS, t-PA antigen (10.5 (8.3-13.9) vs. 11.5 (8.8-15.0) μg/l; p=0.025) and protein C (108.0±24.1% vs. 118.0±25.7%; p=0.004) were decreased. All parameters except for protein C were predictive for mortality in AS. Fully adjusted hazard ratios (95% CI) were 1.14 (1.04-1.25), 1.19 (1.06-1.34), and 1.29 (1.11-1.49) per 1SD increase for D-dimer, t-PA, and PAI-1, respectively. Including fibrinolysis parameters in risk prediction models for mortality improved the area-under-the-curve (AUC) significantly compared with the conventional risk factors. In conclusion, we found alterations in the fibrinolytic system in smokers, which were more pronounced in male AS. PAI-1, t-PA and D-dimers were significant predictors of mortality in AS in LURIC and should be included into the assessment of cardiovascular risk particularly in patients at risk.

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Section: Discussionmentioning

confidence: 99%

Plasma Fibrinolysis Parameters in Smokers and Non-smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study

Delgado

Siekmeier

Krämer

et al. 2015

Advances in Experimental Medicine and Biology

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“…[1–9] Smoking is known to cause increased fibrinogen concentrations and platelet aggregability, along with impaired fibrinolytic activity, decreased coronary flow reserve, and increased vasospasm. [1213] Recurrent exposure to cigarettes with subsequent catecholamine surges damage endothelial cells, leading to endothelial dysfunction and injury of the vascular intima. Autopsy studies in young adults have showed that the extent of fatty-streak lesions in the coronary arteries of young adults was higher in smokers than in nonsmokers.…”

Section: Discussionmentioning

confidence: 99%

Acute coronary syndrome in young adults from Oman: Results from the gulf registry of acute coronary events

et al. 2010

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Objective:To assess the prevalence, risk factors, presenting features, and in-hospital outcomes of acute coronary syndrome (ACS) patients ≤40 years of age from Oman.Methods:Data were analyzed from 1579 consecutive ACS patients from Oman during May, 2006 to June, 2007, as part of Gulf RACE (Registry of Acute Coronary Events). ACS patients ≤40 years of age were compared with patients >40 years of age.Results:A total of 121 (7.6%) patients were ≤40 years of age with mean age of 36 ± 4 vs. 61 ± 11 years in young and old adults, respectively (P<0.001). More men were seen in the younger age group (81 vs. 60%; P<0.001). Among all the coronary risk factors, young patients had more history of smoking (47 vs. 15%; P<0.001), obesity (72 vs. 58%; P = 0.009), and family history of coronary artery disease (CAD) (16 vs. 7%; P = 0.001). Both groups received aspirin, statins, thrombolytic therapy, and anticoagulants equally; however, younger patients received clopidogrel, glycoprotein IIb/IIIa inhibitors, β-blockers, and in-hospital coronary angiogram more. Younger patients experienced less heart failure (6 vs. 27%; P<0.001) and in-hospital mortality, especially among STEMI patients (0 vs. 10%; P = 0.037).Conclusions:Young ACS patients from Oman have different risk profile. They were treated more aggressively and their outcome was better, which is similar to other populations. However, smoking, along with obesity and family history of CAD were strong risk factors in the young Omani ACS patients. There is a need for prevention programmes to control smoking and obesity epidemic by targeting young adults in the population.

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“…One of the earliest stages of atherogenesis is endothelial dysfunction, which leads to a proinflammatory and prothrombotic phenotype of the endothelium4 and thus provokes the attachment and the subsequent migration of leukocytes. In this context, vascular dysfunction in smokers has been widely described 5 6…”

Section: Introductionmentioning

confidence: 99%

Critical role of fractalkine (CX₃CL1) in cigarette smoke-induced mononuclear cell adhesion to the arterial endothelium

Rius

Piqueras

Cerdá-Nicolás

et al. 2012

Thorax

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Background Cigarette smoking is an important risk factor for the development of cardiovascular disease, yet the pathways through which this may operate are poorly understood. Therefore, the mechanism underlying cigarette smoke (CS)-induced arterial endothelial dysfunction and the potential link with fractalkine/ CX 3 CL1 upregulation were investigated. Methods and results Stimulation of human arterial umbilical endothelial cells (HUAECs) with pathophysiological concentrations of CS extract (1% CSE) increased CX 3 CL1 expression. Neutralisation of CX 3 CL1 activity under dynamic flow conditions significantly inhibited CSE-induced mononuclear cell adhesion to HUAECs (67%). The use of small interfering RNA (siRNA) revealed that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 5 (Nox5) but not Nox2 or Nox4 is the main NADPH isoform involved in CSE-induced CX 3 CL1 upregulation and mononuclear cell arrest. Knock down of HUAEC tumour necrosis factor α expression with siRNA or pharmacological inhibition of p38 mitogen-activated protein kinase and nuclear factor κB also abolished these responses. Interestingly, circulating monocytes and lymphocytes from patients with chronic obstructive pulmonary disease (COPD) (n=29) versus age-matched controls (n=23) showed CX 3 CR1overexpression. Furthermore, CX 3 CL1 neutralisation dramatically diminished their enhanced adhesiveness to CSE-stimulated HUAECs. Finally, when animals were exposed for 3 days to CS, a mild inflammatory response in the lung was observed which was accompanied by enhanced CX 3 CL1 expression in the cremasteric arterioles, an organ distant from the lung. CS exposure resulted in increased leukocyte-arteriolar endothelial cell adhesion which was significantly reduced (51%) in animals lacking CX 3 CL1 receptor (CX 3 CR1). Conclusions These results suggest that CS induces functional CX 3 CL1 expression in arterial endothelium and leukocytes from patients with COPD show increased CX 3 CL1-dependent adhesiveness. Therefore, targeting the CX 3 CL1/CX 3 CR1 axis might prevent COPD-associated cardiovascular disorders.

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Marked Impairment of Protease-Activated Receptor Type 1-Mediated Vasodilation and Fibrinolysis in Cigarette Smokers

Cited by 23 publications

References 26 publications

Plasma Fibrinolysis Parameters in Smokers and Non-smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study

Plasma Fibrinolysis Parameters in Smokers and Non-smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study

Acute coronary syndrome in young adults from Oman: Results from the gulf registry of acute coronary events

Critical role of fractalkine (CX₃CL1) in cigarette smoke-induced mononuclear cell adhesion to the arterial endothelium

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Marked Impairment of Protease-Activated Receptor Type 1-Mediated Vasodilation and Fibrinolysis in Cigarette Smokers

Cited by 23 publications

References 26 publications

Plasma Fibrinolysis Parameters in Smokers and Non-smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study

Plasma Fibrinolysis Parameters in Smokers and Non-smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study

Acute coronary syndrome in young adults from Oman: Results from the gulf registry of acute coronary events

Critical role of fractalkine (CX3CL1) in cigarette smoke-induced mononuclear cell adhesion to the arterial endothelium

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Critical role of fractalkine (CX₃CL1) in cigarette smoke-induced mononuclear cell adhesion to the arterial endothelium