Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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.
 ...
PMID:Metalloproteinases in degenerative aortic disease. 165 68

Growth plate cartilage from normal and vitamin D-phosphate deficient (-VDP) rats was cultured to study the production of collagenase and tissue inhibitor of metalloproteinases (TIMP) in vitro. All tissues secreted latent collagenase into the medium at a constant rate during the 5 days in culture. Microdissected-VDP growth plates, containing predominatly hypertrophic cells, released up to 8-fold more collagenase into the medium than either intact-VDP or normal growth plates. TIMP was also secreted during the culture, but its rate of production was not as dependent on tissue type as collagenase. The tissue level of collagenase and TIMP before culture was compared with that found in conditioned medium and remnant tissue after culture. During the 5 day culture period microdissected-VDP growth plates, containing predominatly hypertrophic cells, produced 3-times more collagenase/microgram DNA over the starting level than either intact-VDP or normal growth plates. TIMP was never found in tissues after they had been cultured, but was present in all tissues before culture except those containing predominatly hypertrophic cells. The amount of TIMP required to block collagenase was calculated. Growth plates in culture produced enough TIMP to block all collagenase found in the medium and remnant tissue, while extracts of uncultured intact -VDP growth plates, and those divided to contain hypertrophic cells, had an excess of collagenase over TIMP. The results suggest that hypertrophic cells produce far more collagenase than other cells in the growth plate, but all cell types have about the same capacity to synthesize TIMP. As a result, increased collagenase synthesis by hypertrophic cells may surpass increases in TIMP synthesis and lead to collagen removal. This would allow for thinning of the longitudinal septa and expansion of the hypertrophic cells.
 ...
PMID:Production of collagenase and tissue inhibitor of metalloproteinases (TIMP) by rat growth plates in culture. 196 14

The histopathological changes associated with rotator cuff tears include thinning and disorganization of collagen fibers, the presence of granulation tissue, increased levels of glycosaminoglycans, fibrocartilaginous metaplasia, calcification, fatty infiltration, and necrosis of the tendon margin with cell apoptosis. The biochemical changes include an increase in the expression of matrix metalloproteinases (MMPs) and a decrease in tissue inhibitor of metalloproteinases (TIMP) messenger ribonucleic acid expression. Histological evidence of tendinopathy has been found in patients with rotator cuff tear. Biochemical changes include significant increases in MMP1, MMP2, MMP3, and in TIMP1 and TIMP2 levels, not only at the lateral supraspinatus edge, but also in the macroscopically intact portion of the supraspinatus tendon and in the intact subscapularis. The tissue in the ruptured area of the supraspinatus tendon undergoes marked rearrangement at molecular levels. This involves the activity of MMP1, 2, and 3 and supports a critical role of MMPs in tendon physiology. Intact parts of the torn supraspinatus tendon can present the histopathological changes associated with rotator cuff tears. These findings suggest that biochemical changes can already occur in a macroscopically intact tendon and seem to point to a global degenerative process in the shoulder.
...
PMID:Degenerative disease in rotator cuff tears: what are the biochemical and histological changes? 2560 38