Accelerated enlargement of experimental abdominal aortic aneurysms in a mouse model of chronic cigarette smoke exposure

Buckley, Celine; Wyble, Charles W.; Borhani, Martin; Ennis, Terri L.; Kobayashi, Dale K.; Curci, John A.; Shapiro, Steven D.; Thompson, Robert W.

doi:10.1016/j.jamcollsurg.2004.08.010

Cited by 44 publications

(18 citation statements)

References 41 publications

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“…112 Smoking is a potent risk factor of AAA, 113 and chronic smoke exposure accelerates enlargement of experimental AAA. 114 Interestingly, human peripheral blood mononuclear cells isolated from smokers have elevated IL-4 levels compared with those isolated from nonsmokers. 115 Moreover, cigarette smoke induces IL-4 expression from human aortic ECs, 116 and cigarette smoke extract inhibits IL-2 and IFN-␥ production by peripheral blood mononuclear cells.…”

Section: Triggers For a Cascade Of Events Leading To Atherosclerosis mentioning

confidence: 99%

Inflammation and Cellular Immune Responses in Abdominal Aortic Aneurysms

Shimizu

Mitchell

Libby

2006

ATVB

566

478

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Abstract-Expansion and rupture of abdominal aortic aneurysms (AAA) result in high morbidity and mortality rates. Like stenotic atherosclerotic lesions, AAA accumulate inflammatory cells, but usually exhibit much more extensive medial damage. Leukocyte recruitment and expression of pro-inflammatory Th1 cytokines typically characterize early atherogenesis of any kind, and modulation of inflammatory mediators mutes atheroma formation in mice. 1 However, the mechanistic differences between stenotic and aneurysmal manifestations of atherosclerosis remain unexplained. We recently showed that aortic allografts deficient in interferon-␥ (IFN-␥) signaling developed AAA correlating with skewed Th2 cytokine environments, suggesting important regulatory roles for Th1/Th2 cytokine balance in modulating matrix remodeling and important implications for the pathophysiology of aortic aneurysm and atherosclerosis. Key Words: aortic aneurysm Ⅲ atherosclerosis Ⅲ cytokine Ⅲ pathogenesis Ⅲ T-lymphocytes Ⅲ transplantation A ortic aneurysms are permanent and localized aortic dilations defined as having diameters 1.5-times greater than normal (ie, Ͼ3 cm diameter for abdominal aortic aneurysms [AAA]). In comparison, the term aortic ectasia describes localized aortic enlargement Ͻ1.5-times normal diameter. 2 Although most aneurysms remain asymptomatic and undiagnosed, risk of rupture increases dramatically when diameters exceed 5.5 cm. Despite surgical advances, the prognosis of ruptured AAA remains poor, and the overall mortality remains high (80% to 90%). 3 Although surgical or endovascular repair constitutes the major therapeutic options for AAA Ͼ5.5 cm, such invasive procedures provide no therapeutic advantage for AAA Ͻ5.5 cm diameter.Most AAA develop below the renal arteries and end above the bifurcation of the iliac arteries; they typically exhibit a fusiform morphology, with symmetrical circumferential enlargement involving all layers of the aortic wall. Less frequently, aneurysms have a saccular form, with aneurysmal degeneration affecting only part of the aortic circumference. The AAA wall usually becomes laminated with thrombus and its intraluminal diameter often appears relatively normal by angiography. Important histological features of aneurysms include chronic adventitial and medial inflammatory cell infiltration, elastin fragmentation and degeneration, and medial attenuation. Collagen (especially types I and III) in the media and adventitia provides tensile strength to the aortic wall. Collagen synthesis increases during the early stages of aneurysm formation, suggesting a repair process. 4 However, in later stages, collagen degradation exceeds its synthesis (accompanied by excessive degradation of other extracellular matrix macromolecules, notably elastin), ultimately favoring AAA rupture. Indeed, AAA exhibit increased local production of enzymes capable of degrading collagen and elastin extracellular matrix proteins. [5][6][7] In AAA, inflammatory cells (polymorphonuclear neutrophils, T cells, B cells, macrophages, mast c...

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Section: Triggers For a Cascade Of Events Leading To Atherosclerosis mentioning

confidence: 99%

Inflammation and Cellular Immune Responses in Abdominal Aortic Aneurysms

Shimizu

Mitchell

Libby

2006

ATVB

566

478

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“…2,7,37 Chronic smoke exposure is also associated with substantial increase in progression of aneurysmal dilatation in a mouse model. 38 Conversely, smoking cessation apparently reduces the growth rate of small AAAs in patients with AAA. 39 Interestingly, endothelial cells from internal mammary arteries of patients who are smokers reportedly exhibit higher Angptl2 expression than do cells from nonsmoker and former smoker patients, 40 suggesting that increased Angptl2 expression links cigarette smoking with AAA progression.…”

Section: Downloaded Frommentioning

confidence: 99%

Macrophage-Derived Angiopoietin-Like Protein 2 Accelerates Development of Abdominal Aortic Aneurysm

Tazume¹,

Miyata²,

Tian³

et al. 2012

ATVB

102

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Objective-Recently, we reported that angiopoietin-like protein 2 (Angptl2) functions in various chronic inflammatory diseases. In the present study, we asked whether Angptl2 and its associated chronic inflammation contribute to abdominal aortic aneurysm (AAA). Methods and Results-Immunohistochemistry revealed that Angptl2 is abundantly expressed in infiltrating macrophages within the vessel wall of patients with AAA and in a CaCl 2 -induced AAA mouse model. When Angptl2-deficient mice were used in the mouse model, they showed decreased AAA development compared with wild-type mice, as evidenced by reduction in aneurysmal size, less severe destruction of vessel structure, and lower expression of proinflammatory cytokines and matrix metalloproteinase-9. However, no difference in the number of infiltrating macrophages within the aortic aneurysmal vessel wall was observed between genotypes. AAA development was also significantly suppressed in wild-type mice that underwent Angptl2-deficient bone marrow transplantation. Expression levels of proinflammatory cytokines and metalloproteinase-9 in Angptl2-deficient macrophages were significantly decreased, and those decreases were rescued by treatment of Angptl2 deficient macrophages with exogenous Angptl2. Key Words: abdominal aortic aneurysm n angiopoietin-like protein 2 n chronic inflammation n macrophage n matrix metalloproteinase Conclusions-Macrophage-derived

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“…Some studies suggest that the number of cigarettes currently smoked and the depth of inhalation influence aneurysm formation, 37 whereas others have shown that the duration of exposure rather than the level of exposure determines that risk. 35 Studies in humans and mice showed that besides AAA formation, smoking correlates with increased aneurysmal expansion 38,39 and that quitting smoking could reduce the growth rate of small AAAs. 40 In addition, the UK Small Aneurysm Trial showed that smokers with impaired lung function had an increased risk of aneurysm rupture and poorer long-term survival.…”

Section: Clinical Evidencementioning

confidence: 99%

Smoking and Aortic Diseases

Kakafika

Mikhailidis

2007

Circ J

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Cigarette smoking is a major cause of cardiovascular disease (CVD) and is responsible for approximately 11% of the annual total CVD deaths in the United States. 1 Smoking acts synergistically with other vascular risk factors (eg, hypertension, dyslipidaemia and diabetes) to increase vascular morbidity and mortality. 2 However, smoking has a variable magnitude of increased risk for different vascular diseases: the risk is highest for peripheral arterial disease and aortic aneurysm, and is lowest for coronary artery and cerebrovascular diseases. 2 These effects are thought to reverse after smoking cessation. The constituents of cigarette smoke with the major contribution to pathogenesis of vascular disease are nicotine, carbon monoxide, oxidant gases and polycyclic aromatic hydrocarbons. 2 Nonsmokers who are exposed to "secondhand" smoke experience on average a 30% excess risk of ischemic heart disease and nonfatal myocardial infarction. 3 Secondhand smoke exposure has been shown to activate platelets and to produce endothelial dysfunction, in both experimental animals and humans. 3 The mechanisms by which smoking causes acute cardiovascular events include endothelial dysfunction, thrombosis and inflammation.Endothelial dysfunction is an initiating event in atherogenesis, as well as a major factor in causing acute cardiovascular events. Cigarette smoking impairs flow-mediated endothelium-dependent peripheral arterial vasodilatation, an effect that is, at least partly, reversible after smoking Circulation Journal Vol.71, August 2007 cessation. 4 Smokers without atherosclerosis have coronary vasoconstrictor responses to acetylcholine that, in the presence of normal endothelium, produce vasodilatation. 5 Indeed, the oxidant chemicals of smoke degrade nitric oxide (NO) and reduce NO release, with subsequent impairment of vascular dilation and platelet function. 2 Smokers have lower than normal levels of antioxidant vitamins, reflecting their consumption in response to ongoing oxidant stress. 6 In addition, nicotine itself alters the structural and functional characteristics of vascular smooth muscle cells (VSMC) and endothelial cells. 7,8 Experimental data show that human aortic endothelial cells undergo apoptotic changes when they are exposed to cigarette smoke extracts. 9 This process may be prevented by pre-activation of NO synthase by Larginine. 9,10 Furthermore, smoking causes an increase in vascular superoxide production, which results in decreased NO bioactivity and concomitantly increases production of vasoconstrictor eicosanoids. 11 Cigarette smoke extracts, but not nicotine, also inhibit prostacyclin (PGI2: a vasodilator and inhibitor of platelet aggregation) synthesis in human, rabbit and rat vascular tissue. 12 Smoking-mediated endothelial dysfunction also results in reduced secretion of tissue plasminogen activator (tPA) 13 and increased secretion of plasminogen activator inhibitor (PAI)-1, 1 which results in impaired fibrinolysis. This acts in concert with the increased levels of tissue factor and fibrin...

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Accelerated enlargement of experimental abdominal aortic aneurysms in a mouse model of chronic cigarette smoke exposure

Cited by 44 publications

References 41 publications

Inflammation and Cellular Immune Responses in Abdominal Aortic Aneurysms

Inflammation and Cellular Immune Responses in Abdominal Aortic Aneurysms

Macrophage-Derived Angiopoietin-Like Protein 2 Accelerates Development of Abdominal Aortic Aneurysm

Smoking and Aortic Diseases

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