Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.23 (MMP)
 4,246 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abdominal aortic aneurysms are characterized by intimal atherosclerosis, disruption and attenuation of the elastic media, and a variable adventitial inflammatory infiltrate. We have developed an animal model of this disorder to evaluate the contribution of hypercholesterolemia, medial injury, and adventitial inflammation to aneurysmal dilatation. To accomplish this, we used periaortic application of calcium chloride, which induced both medial injury with calcification and endothelial injury. Ultrasonography was used to demonstrate the dilatation and thickening of the aortic wall. Over the first 3 weeks after periaortic application of 0.25 mol/L CaCl2, the external aortic diameter increased from 3.5 +/- 0.5 to 4.2 +/- 0.8 mm, but the ID remained unchanged. This apparent wall thickening was accompanied by vascular remodeling, and biochemical changes included approximately 50% reduction in tissue hydroxyproline concentration and increased activity of gelatinases (matrix metalloproteinase [MMP]-2 and MMP-9). Independently, cholesterol feeding to induce hypercholesterolemia or the concomitant periaortic application of thioglycollate had little effect on the histological, biochemical, or diameter changes. Together, hypercholesterolemia and thioglycollate were associated with rapid aortic dilatation in CaCl2, treated animals but not controls: after 3 weeks, the ID and OD had doubled, the OD increasing from 3.5 +/- 0.4 to 7.1 +/- 0.4 mm, P = .005. The remarkable feature that accompanied this dilatation was the infiltration of cells, mostly foamy macrophages, into the adventitia, with a further reduction in hydroxyproline concentration. Adventitial inflammation may provide the critical stimulus to dilatation of an aorta with preexisting intimal and medial injury.
 ...
PMID:Influence of hypercholesterolemia and adventitial inflammation on the development of aortic aneurysm in rabbits. 901 31

We have recently demonstrated that promatrix metalloproteinases (proMMPs), particularly proMMP-9, are potent ligands of the leukocyte beta(2) integrins. We studied here the complex formation between proMMP-9 and alpha(M)beta(2), the major MMP and integrin of neutrophils. On resting neutrophils, the proMMP-9/alpha(M)beta(2) complex was primarily detected in intracellular granules, but after cellular activation it became localized to the cell surface, as demonstrated by immunoprecipitation and double immunofluorescence. Further indication of the complex formation was that neutrophils and alpha(M)beta(2)-transfected L cells, but not the wild-type L cells or leukocyte adhesion deficiency cells, bound to immobilized proMMP-9 or its recombinant catalytic domain in a beta(2) integrin-dependent manner. Peptides that bound to the alpha(M) integrin-I domain and inhibited its complex formation with proMMP-9 prevented neutrophil migration in a transendothelial assay in vitro and in a thioglycolate-elicited peritonitis in vivo. These results suggest that the translocating proMMP-9/alpha(M)beta(2) complex may be part of the cell surface machinery guiding neutrophil migration.
 ...
PMID:Intracellular and cell surface localization of a complex between alphaMbeta2 integrin and promatrix metalloproteinase-9 progelatinase in neutrophils. 1515 28