Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased aortic and liver prolyl hydroxylase activity has been suggested as an early biochemical indicator of the fibrotic changes which occur in rabbits with injury induced arteriosclerosis. Daily administration of epinephrine (0.025-0.050 mg/kg, i.v.) and thyroxine (0.050 mg/kg, i.p.) to rabbits for 3 weeks produced aortic fibrous plaques with a 4-fold increase in aortic prolyl hydroxylase and also a 5-fold increase in liver prolyl hydroxylase. Histopathologically, the livers of these rabbits show subcapsular areas of necrosis. When total prolyl hydroxylase related antigen was measured. the increase in liver prolyl hydroxylase activity accounted for only a small portion of the total prolyl hydroxylase antigen. However, in the aorta a majority of the increase in antigen is due to the increased amount of enzyme. DNA content per aorta was unchanged and RNA content increased in the aortic tissue of the arteriosclerotic rabbits. However DNA and RNA levels increased 60% in the livers of arteriosclerotic rabbits. In vitro incorporation of radioactively labeled proline into collagenase digestable protein was at least 2-fold greater in aorta and liver minces from arteriosclerotic rabbits. Michaelis--Menten kinetic parameters were obtained for the liver prolyl hydroxylase purified by affinity chromatography from arteriosclerotic rabbits. The Km for the enzyme from treated animals was not significantly different from control. However, the Vmax of the enzyme purified from diseased liver was 4-fold greater when compared to controls.
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PMID:Increased collagen synthesis and the kinetic characteristics of prolyl hydroxylase in tissues of rabbits with experimental arteriosclerosis. 18

Synthetic activity of collagen types was examined in cultured arterial smooth muscle cells during modulation from synthetic to contractile phenotype by treatment with dimethyl sulfoxide (DMSO). Smooth muscle cells of rabbit thoracic aorta cultured with a 1% supplement of DMSO for 8 days (DMSO group) predominantly exhibited cellular features of the contractile type with abundant microfilaments and a distinct basement membrane. Cultured cells in the DMSO group or in controls during stationary or subconfluent phase were labeled with [3H]proline for 24 h, and the samples including the cell layer and medium were analyzed. The incorporation of proline into bacterial collagenase-digestible fractions was increased slightly in the DMSO group. Type analysis of the collagenous protein by SDS-PAGE and subsequent fluorography disclosed a markedly increased ratio of type IV/I collagen and a slightly increased type V/I collagen ratio, as compared with those of controls. A decrease of type III collagen production in DMSO-treated cells probably due to their lower cell density was also recognized. From these biochemical and morphological observations, it is suggested that increased synthesis of minor collagen types, particularly type IV collagen, is closely associated with smooth muscle phenotypic expression following DMSO treatment. Similar cellular events may occur in smooth muscle cells migrating into the intima during the process of arteriosclerosis in vivo.
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PMID:Altered synthesis of collagen types in cultured arterial smooth muscle cells during phenotypic modulation by dimethyl sulfoxide. 265 78

Young pigs raised on a copper-deficient diet develop severe abnormalities of connective tissue due to defective cross-linking of collagen and elastin. They eventually succumb to anemia and cardiovascular damage, the latter apparently due to the defective connective tissue metabolism. We evaluated the effects of nutritional copper deficiency upon collagen and elastin synthesis using short-term explant cultures of the medial portion of four successive segments of the descending aorta from 110-day-old pigs raised on a copper-deficient diet. Collagen synthesis was evaluated by collagenase susceptibility, and elastin synthesis was quantified by immunoprecipitation with an antiporcine-elastin antiserum. In the normal developing aorta, elastin synthesis was maximal in the upper thoracic aorta, while levels of collagen synthesis were highest in the lower abdominal aorta. Both activities subsided by 110 days postpartum. Compared with controls, the copper-deficient group showed: 1) histopathologic changes confined to the luminal half of the thoracic aorta; 2) a 1.3- to 1.6-fold increase in cellularity along the entire length of the organ; 3) a 1.3- to 2.4-fold increase in relative collagen synthesis, the greatest change occurring in the thoracic portion; 4) a 3- to 4-fold increase of relative elastin synthesis in the thoracic aorta, the abdominal aorta remaining unchanged; 5) 4- to 10-fold increases in collagen production; and 6) a greater than 15-fold increase in elastin production by the tissue of the thoracic aorta.(ABSTRACT TRUNCATED AT 250 WORDS)
Arteriosclerosis
PMID:Induction of increased collagen and elastin biosynthesis in copper-deficient pig aorta. 394 64

Endothelium was isolated from samples of aorta and vena cava obtained from cadaver donors at the time kidneys were harvested for transplantation. Digestion with collagenase and gentle swabbing were used to free the cells from the intimal surface. Low density seeding permitted isolation of individual colonies with typical endothelial morphology. Modified Medium 199 supplemented with 10%-20% human plasma-derived serum and an extract from the bovine hypothalamus (500 micrograms/ml) enabled subcultured colonies to grow to confluency when culture surfaces were coated with fibronectin (1 micrograms/cm2). The presence of Factor VIII antigen was demonstrated using an indirect immunofluorescence technique. A monoclonal antibody to cultured umbilical vein endothelium, specific for endothelium, reacted with the subcultured cells from the aorta and vena cava. Type IV procollagen, fibronectin, and thrombospondin were identified as labeled proteins secreted by cultures of adult endothelium that had been incubated with 3H-proline and 3H-glycine. When the cultured endothelium was used in a sodium-m-periodate stimulated T lymphocyte mitogenic culture system, the endothelium exhibited accessory cell function. Prostacyclin production stimulated by incubation with arachidonic acid and PGH2 was variable from vessel to vessel. However, average values were lower than normally seen with cultured primary umbilical vein endothelium.
Arteriosclerosis
PMID:Properties of cultured endothelium from adult human vessels. 636 32

A cylindrical segment, free of complex atherosclerotic lesions, was resected at autopsy from each of 59 descending human thoracic aortas by cutting just below the level of the first pair of intercostal arteries and 35 mm distal to this incision. Each isolated tunica media was defatted and subjected to successive treatment with EDTA-Tris, 5 M guanidine hydrochloride-Tris, 5 M guanidine hydrochloride-Tris-DTE, collagenase and either trypsin or hot alkali. After each extraction or digestion, the dimensions and weight of the segments were measured and the extracted materials were analyzed and quantitated. This allowed the total content of the various components of the tunica media to be assessed by both gravimetric and analytical means. An age-related rise was observed in the total content of the following components: proteins and glycoproteins soluble in chaotropic solvents (ranging from 24 mg/cm in the youngest samples to 46 mg/cm in the oldest) and collagen (38 mg/cm to 69 mg/cm). In contrast, the total content of elastin remained constant at 70 mg/cm at all ages, but its concentration decreased due to the rise in the concentration of the other tissue components as the tunica media thickened with age. It was also noted that with increasing age there was an accumulation of protein(s) which could not be solubilized by extraction with chaotropic agents or with collagenase, but which could be removed by treatment with either trypsin or hot alkali. Mechanical measurements conducted before and after trypsin digestion on samples previously subjected to purification with the first four agents used suggest that this accumulated protein(s) influenced the elastic response of the tissue to the applied stress by increasing the incremental modulus, the breaking stress, and the hysteresis. After the removal of this additional protein(s), the mechanical behavior of the elastin component was found to be identical in all samples, irrespective of age. It is therefore proposed that the morphological changes and the stiffening observed in the aging aortic wall are not due to degradation of its elastin network but to variations in the supramolecular organization of connective tissue components.
Arteriosclerosis
PMID:Age-related changes in composition and mechanical properties of the tunica media of the upper thoracic human aorta. 682 97

The effect of methylmercury (CH3HgCl) on the production of endothelium-derived relaxing factor (EDRF) by cultured human umbilical vascular endothelial cells (HUVECs) based on its anti-aggregatory effect on human platelets was examined. HUVECs were harvested from umbilical veins by collagenase treatment. The platelet aggregation test was performed with cuvettes lined with HUVECs. Platelet aggregation induced by 0.05 units thrombin/ml was inhibited in the presence of HUVECs. This HUVEC-dependent anti-platelet aggregatory effect was enhanced by the addition of bradykinin (10 nmol/L), which stimulates the production of EDRF. Indomethacin (IND, 1 mumol/L) reduced the HUVEC-dependent anti-platelet aggregatory effect. The effect of NG-monomethyl-L-arginine L-NMMA, 100 mumol/L), an inhibitor of nitric oxide synthase (NOS) in endothelial cells, on HUVECs pretreated with IND showed almost complete platelet aggregation similar to results without HUVECs. The anti-platelet aggregatory effect of HUVECs pretreated with IND seemed to depend mainly on EDRF. Methylmercury (MeHg) (20-50 mumol/L) induced dose-dependent platelet aggregation in cuvettes, without HUVECs. Methylmercury (30 mumol/L) induced less platelet aggregation in the presence of HUVECs than in their absence. The degree of inhibitory effect by HUVECs on MeHg-induced platelet aggregation was reduced dose-dependently (30-50 mumol/L MeHg). Methylmercury-induced platelet aggregation at 50 mumol/L MeHg with or without HUVECs was similar. These findings suggest that this simple new experimental system is useful for assessing the production of EDRF by HUVECs, and show that MeHg inhibits the production of EDRF by HUVECs, which may be involved in the etiology of cardiovascular diseases such as hypertension and arteriosclerosis.
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PMID:The effect of methylmercury (CH3HgCl) on the production of endothelium-derived relaxing factor (EDRF) by cultured human umbilical vascular endothelial cells based on its anti-aggregatory effect on human platelets. 878 7

Low density lipoprotein (LDL) apheresis provides both structural and physiologic improvement to the vascular wall. The purpose of this study was to determine whether LDL pheresis alters levels of plasma matrix metalloproteinase-9 (MMP-9) and serum tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). MMP-9 and TIMP-1 were measured in 30 healthy control subjects (Group A), 20 type 2 diabetic hemodialysis patients without obvious arteriosclerosis obliterans (ASO) (Group B), and 20 type 2 diabetic hemodialysis patients with ASO (Group C). Hemodialysis patients were dialyzed three times weekly with a bicarbonate dialysate. Twelve Group C patients underwent LDL apheresis once weekly for 10 weeks, and changes in plasma MMP-9 and serum TIMP-1 levels because of LDL apheresis were measured. LDL apheresis resulted in a significant decrease in total cholesterol and LDL cholesterol levels (p < 0.01). In addition, LDL apheresis improved clinical symptoms (including cold lower extremity, intermittent claudication, and leg pain) and diminished the size of ulcer/necrosis in all patients. Plasma MMP-9 levels were significantly higher in Group C (76.5 +/- 14.6 ng/ml) than in Group A (31.2 +/- 8.4 ng/ml, p < 0.001) or Group B (58.5 +/- 10.8 ng/ml, p < 0.05). Serum TIMP-1 levels were significantly higher in Group C (360.5 +/- 116.5 ng/ml) than in Group A (142.5 +/- 82.5 ng/ml, p < 0.001) or Group B (254.6 +/- 92.6 ng/ml, p < 0.05). Plasma MMP-9 and serum TIMP-1 levels decreased significantly after LDL apheresis (p < 0.05). However, these levels showed little change in the remaining eight Group C patients who did not undergo LDL apheresis. The data suggested that MMP-9 and TIMP-1 are associated with ASO and that LDL apheresis is effective in reducing plasma MMP-9 and TIMP-1 levels in type 2 diabetic hemodialysis patients with ASO.
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PMID:Effects of low-density lipoprotein apheresis on plasma matrix metalloproteinase-9 and serum tissue inhibitor of metalloproteinase-1 levels in diabetic hemodialysis patients with arteriosclerosis obliterans. 1291 86