Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this paper is to examine the impact of endograft material on the inflammatory response after elective endovascular abdominal aortic aneurysm repair. Consecutive patients (n = 22, all men, 53 to 82 years old) were divided into 2 groups according to the graft material used: In group A (n = 12) the endovascular device was made of polyester and in group B (n = 10) the device was made of expanded polytetrafluoroethylene (ePTFE). All patients received antiinflammatory drugs in the perioperative period. Fever, white blood cells and platelet count, serum concentrations of cytokines (interleukin 6 [IL-6], tumor necrosis factor alpha [TNF-alpha], interleukin 8 [IL-8], acute-phase proteins high-sensitivity C-reactive protein [hsCRP] and alpha1-antitrypsin [alpha1-antitrypsin]), and complement protein (C3a) were measured preoperatively and 1, 3, 6, 24, 48, and 72 hours after aneurysm exclusion. One patient in each group had a systemic inflammatory response syndrome with 2 of the systemic inflammatory response syndrome (SIRS) criteria. No other complication associated with inflammation were present in any patient. Fever was more frequent in group A patients. Increases of white blood cells and serum concentrations of IL-6, TNF-alpha, hsCRP, alpha1-antitrypsin, and C3a and decrease of platelet count were recorded in both groups, but no statistically significant difference between them was recorded. However, serum concentrations of IL-8 were significantly higher in group A patients 24 hours postoperatively (p = 0.01). No significant difference was apparent in the biological response between patients receiving a polyester or an ePTFE stent graft, except for fever and serum concentrations of IL-8.
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PMID:Impact of endograft material on the inflammatory response after elective endovascular abdominal aortic aneurysm repair. 1632 51

Abdominal aortic aneurysm (AAA) is a complex inflammatory vascular disease. There are currently limited treatment options for AAA when surgery is inapplicable. Therefore, insights into molecular mechanisms underlying AAA pathogenesis may reveal therapeutic targets that could be manipulated pharmacologically or biologically to halt disease progression. Using an elastase-induced AAA mouse model, we previously established that the complement alternative pathway (AP) plays a critical role in the development of AAA. However, the mechanism by which complement AP is initiated remains undefined. The complement protein properdin, traditionally viewed as a positive regulator of the AP, may also initiate complement activation by binding directly to target surfaces. In this study, we sought to determine whether properdin serves as a focal point for the initiation of the AP complement activation in AAA. Using a properdin loss of function mutation in mice and a mutant form of the complement factor B protein that produces a stable, properdin-free AP C3 convertase, we show that properdin is required for the development of elastase-induced AAA in its primary role as a convertase stabilizer. Unexpectedly, we find that, in AAA, natural IgG antibodies direct AP-mediated complement activation. The absence of IgG abrogates C3 deposition in elastase-perfused aortic wall and protects animals from AAA development. We also determine that blockade of properdin activity prevents aneurysm formation. These results indicate that an innate immune response to self-antigens activates the complement system and initiates the inflammatory cascade in AAA. Moreover, the study suggests that properdin-targeting strategies may halt aneurysmal growth.
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PMID:Antibody directs properdin-dependent activation of the complement alternative pathway in a mouse model of abdominal aortic aneurysm. 2230 31

Abdominal aortic aneurysm (AAA) is a common vascular disease associated with high mortality rate due to progressive enlargement and eventual rupture. There is currently no established therapy known to alter the rate of aneurysmal expansion. Thus, understanding the processes that initiate and sustain aneurysmal growth is pivotal for the development of medical therapies aimed at halting disease progression. Using an elastase-induced AAA mouse model that recapitulates key features of human AAA, we previously reported that a natural IgG antibody directs alternative pathway complement activation and initiates the inflammatory process that culminates in aneurysmal development. The target of this natural antibody, however, was unknown. Herein we identify a natural IgG that binds to fibrinogen deposited in elastase-perfused aortic tissues, activates the complement lectin pathway (LP), and induces AAA. Moreover, we establish that alterations in the glycosylation patterns of this antibody critically affect its ability to activate the LP in vivo. We find that LP activation precedes the alternative pathway and absence of the LP complement protein mannan-binding lectin abrogates elastase-induced AAA. In human AAA tissues the mouse anti-fibrinogen antibody recognizes epitopes that localize to the same areas that stain positively for mannan-binding lectin, which suggests that the complement LP is engaged in humans as well. Lastly, we demonstrate that circulating antibodies in a subset of AAA patients react against fibrinogen or fibrinogen-associated epitopes in human aneurysmal tissues. Our findings support the concept that an autoimmune process directed at aortic wall self-antigens may play a central role in the immunopathogenesis of AAA.
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PMID:Fibrinogen-specific antibody induces abdominal aortic aneurysm in mice through complement lectin pathway activation. 2416 62