Inflammation and Cellular Immune Responses in Abdominal Aortic Aneurysms

Abstract

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...

Association of the polymorphisms of MMP-9 and TIMP-3 genes with thoracic aortic dissection in Chinese Han population

“…For example, the MMP-9 SNP rs3918241 was found to be in strong LD with rs2274768 (D′=1.0, r 2 =0.97) [13] , and the promoter SNP rs3918241 was located within the core sequence of a GATA motif (GTAAAGGAAG[T/A]TAATTATCTC) that could bind GATA factors, which are master regulatory transcription factors important for the perpetuation and differentiation of human Th2 cells. Furthermore, several studies have suggested important regulatory roles for the Th1/Th2 cytokine balance in matrix remodeling and the pathogenesis of atherosclerosis and aortic aneurysm [23] .…”

Dietary salt intake is related to inflammation and albuminuria in primary hypertensive patients

“…[9][10][11][12][13] The role of inflammation in the initiation and progression of cardiovascular diseases is increasingly recognized. 14,15 Studies in hypertensive individuals have shown increased plasma and vascular tissue levels of C-reactive protein (CRP) and several inflammatory cytokines, suggesting a potential association between vascular inflammation and hypertension. [16][17][18][19] Although the evidence for a direct relationship between salt intake and BP is basically established, [20][21][22][23] the clinical evidence is not adequate to consider whether this effect translates into increased incidence of cardiovascular diseases independent from BP in patients with high dietary salt consumption.…”

T lymphocytes and aortic aneurysms

“…In addition, there are several types of aneurysms and the pathogenesis of them is different [3]. The stage and size of aneurysm may also contribute to the degree of elastin and collagen degradation [12], followed by different CD4 + T cells infiltration including a Th1/Th2 balance or a shift to Th1/Th2.…”

“…Atherosclerosis may not directly cause AAA, but can trigger the first inflammation to induce the infiltrates. The underlying causes could be atherosclerosis, tobacco smoking, familial clustering, genetic background and environmental factors [9,12].…”