scholarly journals Mast Cell Tryptase Deficiency Attenuates Mouse Abdominal Aortic Aneurysm Formation

2011 ◽  
Vol 108 (11) ◽  
pp. 1316-1327 ◽  
Author(s):  
Jie Zhang ◽  
Jiusong Sun ◽  
Jes S. Lindholt ◽  
Galina K. Sukhova ◽  
Mark Sinnamon ◽  
...  
Keyword(s):  
Mast Cell ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Mast Cell Tryptase ◽  
Aneurysm Formation ◽  
Abdominal Aortic

Abstract: S2-17 CRITICAL ROLE OF MAST CELL CHYMASE IN MOUSE ABDOMINAL AORTIC ANEURYSM FORMATION

2009 ◽  
Vol 10 (2) ◽  
pp. e1517
Author(s):  
J Sun ◽  
J Zhang ◽  
J Lindholt ◽  
G Sukhova ◽  
P Libby ◽  
...  
Keyword(s):  
Mast Cell ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Critical Role ◽  
Aneurysm Formation ◽  
Abdominal Aortic ◽  
Mast Cell Chymase

scholarly journals Critical Role of Mast Cell Chymase in Mouse Abdominal Aortic Aneurysm Formation

Circulation ◽  
2009 ◽  
Vol 120 (11) ◽  
pp. 973-982 ◽  
Author(s):  
Jiusong Sun ◽  
Jie Zhang ◽  
Jes S. Lindholt ◽  
Galina K. Sukhova ◽  
Jian Liu ◽  
...  
Keyword(s):  
Mast Cell ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Critical Role ◽  
Aneurysm Formation ◽  
Abdominal Aortic ◽  
Mast Cell Chymase

Abstract 286: Loss of Smad3 Exacerbates Abdominal Aortic Aneurysm Formation With Enhanced Inflammation in an Experimental Mouse Model

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Xiaohua Dai ◽  
Anandita Arora ◽  
Jianbin Shen ◽  
Hong Jiang ◽  
Li Li
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Calcium Chloride ◽  
The United States ◽  
Protective Role ◽  
Elastic Fibers ◽  
Aneurysm Formation ◽  
Abdominal Aortic ◽  
The Media ◽  
Chloride Treatment

Introduction Abdominal aortic aneurysm (AAA) is a complex vascular disease that causes more than 10,000 deaths each year in the United States. Extensive studies have been performed in search of pharmaceutical treatment but surgical repair still remains the most effective treatment. TGF-β signaling is an important mechanism in the pathogenesis of aneurysms; however, there is debate as to whether its role is protective or destructive. Smad3 is a major intracellular mediator of the canonical pathway of TGF-β signaling. Hypothesis We hypothesize that Smad3-mediated TGF-β signal pathway plays important roles in the pathogenesis of AAA. Methods To test this hypothesis, we analyze the effects of loss of Smad3 on aneurysm formation in the calcium chloride induced AAA model using Smad3 knockout mice. Results Three weeks after calcium chloride treatment, the abdominal aorta displayed increased dilation, forming aneurysms. Histology and immunohistochemistry analyses show increased cell proliferation and enhanced inflammatory cell infiltration in the media and adventitia of the vessel wall. This was accompanied by elastic fibers degradation, increased MMPs expression and reduced expression of smooth muscle markers. Further analysis showed that the expression and nuclear localization of Smad2 and Smad4 was significantly increased. Conclusions These results demonstrate that Smad3-mediated TGF-β signaling plays a protective role in the pathogenesis of AAA and Smad2/Smad4 upregulation is not sufficient to compensate for the loss of Smad3 in this experimental model.

Abstract 3718: MMP-12 Inhibitor Reduces Severity of ANGII-induced Aortic Abdominal Aneurysms in apoE−/− Mice

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Dawn A Savio ◽  
Anita R Halpern ◽  
Yuchuan Wu ◽  
Wei Li ◽  
Joseph Sypek ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Vascular Wall ◽  
Inflammatory Disorder ◽  
Gene Markers ◽  
Genetic Ablation ◽  
Macrophage Recruitment ◽  
Aneurysm Formation ◽  
Abdominal Aortic

Abdominal aortic aneurysm (AAA) is an inflammatory disorder characterized by local connective tissue degradation, macrophage recruitment and infiltration leading to aortic dilation and rupture. Aneurysms of the abdominal aorta represent a significant cardiovascular risk for which inflammation plays an integral role in the defined pathology. Genetic ablation of metalloprotease-12 (MMP-12) eliminates metalloelastase activity and attenuates aneurysm formation in apoE−/− mice. In the current study, a selective MMP-12 inhibitor, WAY-644 was evaluated in the well-established murine model of ANGII-induced aneurysm formation. This inhibitor displays activity for murine MMP-12, IC50 = 6.3 nM by FRET analysis, with low crossreactivity for other MMPs (exception MMP-8), and has established in vivo efficacy in inflammation models. Coadministration of WAY-644 to hyperlipidemic apoE−/− mice during ANGII infusion (1.44 mg/kg) for 28d alters the severity of AngII-induced AAAs as measured by changes in abdominal aortic wet weights and typical AAA classification. As expected, plasma MMP-12 protease activity measured by FRET analysis was inhibited. RNA profiling of abdominal aortic aneurysm tissue characterizes ANGII-induced AAA expansion driven by macrophage infiltration, destructive MMP production and attenuation by MMP-12 inhibition. The transcription of a subset of proinflammatory genes activated with ANGII treatment was repressed by the inhibitor. These genes include quantitative markers of macrophage accumulation in the vessel wall, CD68, MCP1/CCL2, CCR2, MMP-12, and Csf1. Associated reductions in gene markers for inflammation and oxidative stress, ie., heme oxidase (HO), nitric oxide synthase (nos2), Ikbkb, and Stat3 also correlate with MMP-12 antagonism. These changes occur in the absence of lipid changes (TC or TG), or quantitative changes in aortic arch lesions in the ANGII-infused animals. The findings support a mechanism whereby MMP-12 metalloelastase inactivation reduces macrophage recruitment to aneurysmal lesion sites, to lessen activated-macrophage expression of proinflammatory cytokines that figure prominently in vascular wall destruction and the pathogenesis of AAAs.

Decreased angiotensin converting enzyme expression and experimental abdominal aortic aneurysm formation

2004 ◽  
Vol 121 (2) ◽  
pp. 324
Author(s):  
M.J. Eagleton ◽  
E. Lynch ◽  
K. Hannawa ◽  
C. Pearce ◽  
D. Woodrum ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Enzyme Expression ◽  
Aneurysm Formation ◽  
Abdominal Aortic
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