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

Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular diseases, but the mechanism is unclear. The pathogenic risk of Lp(a) is associated with elevated plasma concentration, small isoforms of apolipoprotein [apo(a)], the unique apolipoprotein of Lp(a), and a mimic of plasminogen. Inflammation is associated with both the initiation and recovery of cardiovascular diseases, and plasminogen plays an important role in leukocyte recruitment. Because Lp(a)/apo(a) is expressed only in primates, transgenic mice were generated, apo(a)tg and Lp(a)tg mice, to determine whether Lp(a)/apo(a) modifies plasminogen-dependent leukocyte recruitment or whether apo(a) has an independent role in vivo. Plasminogen activation was markedly reduced in apo(a)tg and Lp(a)tg mice in both peritonitis and vascular injury inflammatory models, and was sufficient to reduce matrix metalloproteinase-9 activation and macrophage recruitment. Furthermore, neutrophil recruitment and the neutrophil cytokines, CXCL1/CXCL2, were suppressed in apo(a)tg mice in the abdominal aortic aneurysm model. Reconstitution of CXCL1 or CXCL2 restored neutrophil recruitment in apo(a)tg mice. Apo(a) in the plasminogen-deficient background and Lp(a)tg mice were resistant to inhibition of macrophage recruitment that was associated with an increased accumulation of apo(a) in the intimal layer of the vessel wall. These data indicate that, in inflammation, Lp(a)/apo(a) suppresses neutrophil recruitment by plasminogen-independent cytokine inhibition, and Lp(a)/apo(a) inhibits plasminogen activation and regulates matrix metalloproteinase-9 activation and macrophage recruitment.
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PMID:Lp(a)/apo(a) modulate MMP-9 activation and neutrophil cytokines in vivo in inflammation to regulate leukocyte recruitment. 2465 May 62