Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Atherosclerosis and aneurysm of the abdominal aorta are associated with thinning of the medial connective tissue. We have investigated the presence of the connective-tissue-degrading metalloproteinases in homogenates prepared from atherosclerotic, aneurysmal and control aortic media. 2. Gelatinase activity was much increased in homogenates from atherosclerotic and aneurysmal aorta [10.9 +/- 1.8 and 13.3 +/- 3.3 micrograms of gelatin hydrolysed h-1 (mg of protein)-1 respectively]. This gelatinase activity was highest at the luminal aspect of the aortic media, where the activity increased three- to five-fold after the destruction of alpha 2-macroglobulin. Zymograms demonstrated the principal gelatinase in atherosclerotic aorta to have a molecular mass of about 92 kDa, whereas in aneurysmal aorta there was a spectrum of gelatinase activity from 92 to 55 kDa. 3. Collagenase and stromelysin (proteoglycanase) could be detected by immunoblotting in homogenates of aneurysmal aorta, but rarely in atherosclerotic aorta and never in control aorta. Collagenase and stromelysin activities were low, but increased two- to three-fold after the destruction of tissue inhibitor of metalloproteinases. Collagenase and stromelysin activities were highest at the adventitial aspect of aneurysmal media. 4. The secretion of gelatinase by inflammatory cells at the intima of diseased aorta could have a pathological role in establishing atherosclerotic plaques and medial thinning. Secretion of collagenase, gelatinase and stromelysin from the adventitia could accelerate connective tissue degradation in the media of aneurysmal aorta.
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PMID:Metalloproteinases in degenerative aortic disease. 165 68

Lung epithelial and mesenchymal cells are separated by a basement membrane. At late fetal gestation, this basement membrane in fenestrated, allowing epithelial cytoplasmic extensions to reach in close proximity of the interstitial fibroblast. The enzymes responsible for this focal basement membrane remodelling, and their cellular origin, remains to be defined. Basement membrane remodelling generally involves a special class of matrix-degrading enzymes, called metalloproteinases. Herein, we report that fetal lung cells originating from both tissue layers, mesoderm and endoderm, express the metalloproteinase genes, MMP-1 or interstitial collagenase, and MMP-3 or stromelysin. The inhibitor of metalloproteinases, TIMP-1, is mainly expressed in fetal lung fibroblasts. During late fetal development, MMP-1 mRNA expression in both cell types increases close to term (day 21, term = 22 days), while that of stromelysin and TIMP-1 remain constant. Both fibroblasts and epithelial cells express fibronectin (FN) mRNA. The expression of the FN gene in epithelial cells decreases slightly at the canalicular stage of lung development (days 19-20), whereas FN expression in fibroblasts is not changed with advancing gestation. Procollagen alpha 1 (I) mRNA is predominantly detected in fibroblasts whereas message for laminin B1 chain is primarily found in epithelial cells. Expression of procollagen alpha 1 (I) mRNA decreases in fibroblasts during the canalicular stage of fetal lung development compared to the pseudoglandular stage (day 18) but increases thereafter at the saccular stage (day 21) of development. Laminin B1 expression in epithelial cells declines with advancing gestation. These data are consistent with a process of basement membrane thinning during the canalicular stage, followed by metalloproteinase-mediated penetration. Further, a progressive reduction in laminin expression is consistent with progressive epithelial differentiation.
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PMID:Ontogeny of extracellular matrix gene expression by rat lung cells at late fetal gestation. 948 4

We studied whether rapid thinning of large pulmonary arteries of neonatal rats is associated with breakdown of collagen. Pulmonary artery extracts from fetal to 21 days of age were assayed for collagen content and matrix metalloproteinases. Within 3 days postpartum, no changes in collagen content, collagenolytic activity, or levels of stromelysin-l or gelatinase A were observed. After day 3, collagen content and total proteolytic activity increased with little change in matrix metalloproteinase expression. Thus, collagen was not degraded, and the late increases in collagen and total proteolytic activity were probably growth related. Unlike adult rats in which collagen is broken down after reversal of hypoxic pulmonary artery remodeling, collagen is not broken down in neonatal pulmonary arteries during adaptation to extrauterine life.
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PMID:Remodeling of rat neonatal pulmonary artery: role of matrix metalloproteinases. 1032 39

Clinical complications of atherosclerosis are often triggered by the rupture of unstable plaques, while thinning of the atherosclerotic vessel wall owing to elastin and collagen degradation and media necrosis may result in aneurysm formation and bleeding. Proteolysis, mediated via the plasminogen/plasmin and/or matrix metalloproteinase (MMP) systems may contribute to neovascularization and rupture of plaques, or to ulceration and rupture of aneurysms. In an in vivo model of atherosclerosis, using mice that had a combined deficiency of apolipoprotein E (ApoE) and urokinase-type plasminogen activator (u-PA) and that were maintained on a cholesterol-rich diet, it was observed that u-PA deficiency protects against aneurysm formation. This was explained by the findings that plasmin, generated from plasminogen by u-PA, activates several macrophage-secreted proMMPs (e.g. proMMP-3, -9, -12 and -13), which in turn cause extracellular matrix degradation. A potential role for MMP-3 (stromelysin-1) was confirmed in a subsequent study using mice with a combined deficiency of ApoE and MMP-3, that were kept on a cholesterol-rich diet. The results suggest that MMP-3 contributes to plaque destabilization, possibly by degrading extracellular matrix components, but also promotes aneurysm formation by degrading the elastic lamina. These effects may be mediated by MMP-3 directly or by activation of other proMMPs or other (proteolytic) systems. A functional role of MMPs is further supported by the finding that deficiency in TIMP-1 (tissue inhibitor of MMPs type 1) reduces atherosclerotic plaque size but enhances aneurysm formation. Taken together, these results suggest that u-PA has an important role in the structural integrity of the atherosclerotic vessel wall, which is likely to involve triggering the activation of MMPs and, furthermore, they suggest that increased u-PA levels are a risk factor for aneurysm formation.
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PMID:Extracellular proteolysis in the development and progression of atherosclerosis. 1202 44