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)

Evaluation of: Pagano MB, Bartoli MA, Ennis TL et al.: Critical role of dipeptidyl peptidase I in neutrophil recruitment during the development of experimental abdominal aortic aneurysms. Proc. Natl Acad. Sci. USA 104(8), 2855-2860 (2007). In this study, the authors used dipeptidyl peptidase I (DPPI) gene-targeted mice and an aortic elastase perfusion-induced mouse abdominal aortic aneurysm (AAA) model to examine the role of DPPI, also termed cathepsin C, in the development of AAA. Mice lacking this protease are resistant to AAA formation. Interestingly, these authors found that DPPI activity controls neutrophil recruitment to the sites of inflammation, specifically AAA lesions in this case. By producing chemokine CXCL2, neutrophils in AAA lesions recruit additional neutrophils to the lesion sites where these cells utilize DPPI to activate neutrophil serine proteases, including neutrophil elastase, cathepsin G and proteinase 3, which may be further used to stimulate macrophage cytokine and chemokine production. In addition to DPPI-deficient mice, the authors also used antibodies against neutrophils (Gr-1) or CXCL2 receptor, CXCR2, to deplete neutrophils or to block the action of neutrophil chemokines to affirm their hypothesis.
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PMID:Role of cathepsin C in elastase-induced mouse abdominal aortic aneurysms. 1980 79

Inflammation plays a critical role in the development of abdominal aortic aneurysm (AAA). Chemokine receptor CXCR2 mediates inflammatory cell chemotaxis in several diseases. However, the role of CXCR2 in AAA and the underlying mechanisms remain unknown. In this study, we found that the CXCR2 expressions in AAA tissues from human and angiotensin II (Ang II)-infused apolipoprotein E knockout (Apo E-/-) mice were significantly increased. The pharmacological inhibition of CXCR2 (SB265610) markedly reduced Ang II-induced AAA formation. Furthermore, SB265610 treatment significantly reduced collagen deposition, elastin degradation, the metal matrix metalloprotease expression and accumulation of macrophage cells. In conclusion, these results showed CXCR2 plays a pathogenic role in AAA formation. Inhibition of CXCR2 pathway may represent a novel therapeutic approach to treat AAA.
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PMID:Chemokine (C-X-C motif) receptor 2 blockade by SB265610 inhibited angiotensin II-induced abdominal aortic aneurysm in Apo E-/- mice. 3053 55