Effects of Cigarette Smoking on the Ultrastructure of Rat Thoracic Aorta and Its Ability to Produce Prostacyclin

Pittilo, R. M.; Mackie, Ian; Rowles, P M; Machin, Samuel J.; Woolf, N. J.

doi:10.1055/s-0038-1657250

Cited by 117 publications

(26 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…CS exposure has been shown by immunogold electron microscopy to induce the upregulation of P32-integrin adhesion molecules on leukocytes sequestered in the upper lobes of rabbit lungs (31), to reduce leukocyte deformability (43), and to increase in rats and humans the production by endothelial cells of proaggregatory thromboxane while at the same time inhibiting the generation of antiaggregatory prostacyclin (30). Whether these effects of CS are ROS-dependent and could thus be affected by vitamin C remains to be shown.…”

Section: Resultsmentioning

confidence: 99%

Vitamin C prevents cigarette smoke-induced leukocyte aggregation and adhesion to endothelium in vivo.

Lehr¹,

Frei²,

Arfors³

1994

Proc. Natl. Acad. Sci. U.S.A.

152

View full text Add to dashboard Cite

A common feature of cigarette-smoke (CS)-associated diseases such as atherosclerosis and pulmonary emphysema is the activation, aggregation, and adhesion of leukocytes to micro-and macrovascular endothelium. A previous study, using a skinfold chamber model for intravial fluorescence microscopy in awake hamsters, has shown that exposure of hamsters to the smoke generated by one research cigarette elicits the adhesion of fluorescently labeled leukocytes to the endothelium of arterioles and small venules. By the combined use of intravital microscopy and scanning electron microscopy, we now demonstrate in the same animal model that (i) CS-induced leukocyte adhesion is not confined to the microcirculation, but that leukocytes also adhere singly and in clusters to the aortic endothelium; (ii) CS induces the formation in the bloodstream of aggregates between leukocytes and platelets; and (iii) CS-induced leukocyte adhesion to micro-and macrovascular endothelium and leukocyte-platelet aggregate formation are almost entirely prevented by dietary or intravenous pretreatment with the water-soluble antioxidant vitamin C (venules, 21.4 ± 11.0 vs. 149.6 ± 38.7 leukocytes per mm2, P < 0.01; arterioles, 8.5 ± 4.2 vs. 54.3 ± 21.6 leukocytes per mm2, P < 0.01; aortas, 0.8 ± 0.4 vs. 12.4 ± 5.6 leukocytes per mm2 P < 0.01; means ± SD of n = 7 animals, 15 min after CS exposure). No inhibitory effect was observed by pretreatment of the animals with the lipid-soluble antioxidants vitamin E or probucol. The protective effects of vitamin C on CSinduced leukocyte adhesion and aggregation were seen at vitamin C plasma levels (55.6 ± 22.2 spM, n 7) that can easily be reached in humans by dietary means or supplementation, suggesting that vitamin C effectively contributes to protection from CS-associated cardiovascular and pulmonary diseases in humans.Cigarette smoke (CS) has been identified as an independent major risk factor for the development of pulmonary and cardiovascular diseases, such as chronic obstructive pulmonary disease, emphysema, atherosclerosis, and coronary artery disease (1). Although the spectrum of adverse effects of CS involves multiple tissue and organ systems, a feature common to the pathomechanism of most CS-associated diseases is the activation and adhesion of circulating leukocytes to micro-and/or macrovascular endothelium (2-4), followed by acute and/or chronic leukocyte-mediated tissue damage (5, 6). In agreement with earlier reports on the sequestration and activation of leukocytes in the pulmonary microcirculation in rabbits (7), hamsters (8, 9), and humans (10), intravital microscopy in a skinfold chamber model in hamsters revealed that the exposure of hamsters to the smoke of one cigarette elicits the rolling and adhesion of fluorescently labeled leukocytes to the endothelium of small venules and arterioles in striated muscle (11). Leukocyte adhesion was significantly reduced by pretreatment of the animals with superoxide dismutase, implying a key mediator role for superoxide radicals in CS-induced leu...

show abstract

Section: Resultsmentioning

confidence: 99%

Vitamin C prevents cigarette smoke-induced leukocyte aggregation and adhesion to endothelium in vivo.

Lehr¹,

Frei²,

Arfors³

1994

Proc. Natl. Acad. Sci. U.S.A.

152

View full text Add to dashboard Cite

show abstract

“…First, cigarette smoke contains high level of free radicals, and the scavenging activity of cigarette smoke-derived free radicals leads to reduced NO bioavailability. 17,20,21 Second, altered endothelial NO synthase protein and its activity also decrease NO availability in relation to cigarette smoker exposure. 16,17,19 Not only is NO a vasoregulatory molecule but also it helps regulate inflammation, leukocyte adhesion, platelet activation, and thrombosis.…”

Section: Coronary Thrombosis In Cigarette Smoke Exposure 1461mentioning

confidence: 99%

“…It was reported that aortas from rats that were chronically exposed to cigarette smoke showed a reduction in PGI 2 production. 21 Reinders et al 22 showed that incubation of cultured HUVECs with cigarette smoke condensate impaired the basal and stimulated (phorbol myristate acetate) production of PGI 2 . Ahlsten et al 23 reported that maternal smoking significantly decreased PGI 2 production in umbilical arteries from newborn infants.…”

Section: Coronary Thrombosis In Cigarette Smoke Exposure 1461mentioning

confidence: 99%

Mechanisms of Coronary Thrombosis in Cigarette Smoke Exposure

Barua

Ambrose

2013

ATVB

198

126

View full text Add to dashboard Cite

Abstract-Acute rupture or erosion of a coronary atheromatous plaque and subsequent coronary artery thrombosis cause the majority of sudden cardiac deaths and myocardial infarctions. Cigarette smoking is a major risk factor for acute coronary thrombosis. Indeed, a majority of sudden cardiac deaths attributable to acute thrombosis are in cigarette smokers. Both active and passive cigarette smoke exposure seem to increase the risk of coronary thrombosis and myocardial infarctions. Cigarette smoke exposure seems to alter the hemostatic process via multiple mechanisms, which include alteration of the function of endothelial cells, platelets, fibrinogen, and coagulation factors. This creates an imbalance of antithrombotic/ prothrombotic factors and profibrinolytic/antifibrinolytic factors that support the initiation and propagation of thrombosis.

show abstract

“…'9 Platelets have been shown in vitro to augment this response. 9 We demonstrated an association between current smoking and thrombosis complicating PTCA. Nicotine has been shown to inhibit vascular prostacyclin, but not platelet thromboxane production.…”

Section: Discussionmentioning

confidence: 69%

“…Other factors, such as smoking, may alter endothelial competence and promote platelet reactivity. [8][9][10] We hypothesized that pretreatment with effective antiplatelet therapy would decrease the incidence or severity of thrombus formed at the angioplasty site. We designed the following retrospective study to assess the association of pretreatment with aspirin (with or without dipyridamole) with a decreased incidence of acute coronary thrombosis complicating routine PTCA.…”

mentioning

confidence: 99%

Aspirin and dipyridamole in the prevention of acute coronary thrombosis complicating coronary angioplasty.

Barnathan¹,

Schwartz²,

Taylor³

et al. 1987

Circulation

296

View full text Add to dashboard Cite

To test the hypothesis that pretreatment with adequate antiplatelet therapy reduces the likelihood of acute coronary thrombosis during routine percutaneous transluminal coronary angioplasty (PTCA), we reviewed, blinded to treatment group, the films and records of 300 consecutive initially successful PTCAs. Films before PTCA, immediately after, and at least 30 min after the last balloon inflation were assessed for the presence of any thrombus at the PTCA site. We excluded 37 patients who received streptokinase before PTCA or who had 100% occlusion or thrombus on pre-PTCA films. New thrombi were classified as clinically significant (defined as causing 100% occlusion or requiring emergency surgery or streptokinase therapy) or as not significant (not causing an acute problem or requiring intervention). Patients were classified into three groups, based on the type and extent of antiplatelet therapy received. Group 1 (no aspirin, n = 121) consisted of patients who did not receive aspirin either before admission or in hospital before PTCA (with or without dipyridamole). Group 2 (standard treatment, n = 110) received aspirin with or without dipyridamole but did not receive both drugs before admission and in hospital before PTCA. Group 3 (maximal treatment, n = 32) received both aspirin and dipyridamole before admission and in hospital before PTCA. New thrombi were detected at 39 (14.8%) PTCA sites, of which 15 (5.7% of all PTCA sites) were considered clinically significant. Group 1 had the highest incidence of both thrombus (21.5%) and clinically significant thrombus (10.7%). A reduction was seen in group 2 in thrombus (11.8%; p = .07) and in clinically significant thrombus (1.8%; p = .005). Group 3 had no thrombus (p = .001) and no clinically significant thrombus (p = .04). In addition to inadequate pretreatment with antiplatelet therapy, univariate analyses demonstrated several other risk factors for thrombus: higher percent diameter stenosis before PTCA (p < .008), higher platelet count (p = .013), and current smoking (p = .03). Only higher platelet count (p < .001) and inadequate pretreatment (p = .001) were associated with clinically significant thrombus. Stepwise logistic regression analysis demonstrated that for thrombus, the lack of effective antiplatelet therapy was the most discriminatory variable, followed by current smoking, higher percent diameter stenosis, and dissection. For clinically significant thrombus, once the lack of pretreatment with effective antiplatelet therapy was considered, no other factors added significant discriminatory information. Thus, antiplatelet therapy administered before PTCA is associated with a decreased incidence and significance of acute coronary thrombosis complicating PTCA. The lack of effective antiplatelet therapy before PTCA, as well as current smoking, higher percent diameter stenosis, and dissection, identify patients at risk for this complication.

show abstract

Effects of Cigarette Smoking on the Ultrastructure of Rat Thoracic Aorta and Its Ability to Produce Prostacyclin

Cited by 117 publications

References 9 publications

Vitamin C prevents cigarette smoke-induced leukocyte aggregation and adhesion to endothelium in vivo.

Vitamin C prevents cigarette smoke-induced leukocyte aggregation and adhesion to endothelium in vivo.

Mechanisms of Coronary Thrombosis in Cigarette Smoke Exposure

Aspirin and dipyridamole in the prevention of acute coronary thrombosis complicating coronary angioplasty.

Contact Info

Product

Resources

About