Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.2.2.7 (heparinase)
 1,270 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The ability of heparins (bovine heparin sm 1026, Av. mol. wt. 36.9 kDa and bovine heparin EP 756, Av. mol. wt. 12.9 kDa) and heparin fractions of different molecular weights (low molecular weight heparin, LMW 2123/OP, Av. mol. wt. 4.5 kDa and oligo-heparin, Av. mol. wt. 2 kDa) to inhibit the proliferation and signalling of Balb/c 3T3 fibroblasts was investigated. 2. Heparin and heparin fractions of 4.5 and 2 kDa significantly inhibited DNA synthesis as monitored by [2H]-thymidine incorporation. 3. 3H-labelled heparin fractions of 4.5 and 2 kDa were prepared by gel-chromatography fractionation on Sephadex G-75 of an 3H-labelled commercial heparin after treatment with heparinase. 4. The binding of unfractionated and oligo-heparin of 2 kDa to Balb/c 3T3 fibroblasts was studied; we determined the specificity of heparin and oligo-heparin binding to the cells by means of displacement of bound 3H-labelled compound in response to increasing concentrations of unlabelled compounds. Scatchard analysis of binding data obtained using [3H]-heparin as ligand revealed the presence of a single class of high affinity binding sites (Kd = 28 nM) for heparin. Scatchard analysis of binding data obtained using [3H]-oligo-heparin as ligand revealed the presence of a single class of low affinity binding sites (Kd = 3.2 microM) for oligo-heparin. 5. In addition heparin displaced [3H]-oligo-heparin at a concentration of approximately 100 fold of the Kd determined in displacement studies. Furthermore, oligo-heparin significantly displaced [3H]-heparin at a concentration of approximately 10 fold of the Kd determined by displacement studies. 6. Both heparin and oligo-heparin exert their inhibitory effects on Balb/c 3T3 DNA synthesis stimulated by PDGF or serum. However these molecules did not affect the inositol lipid turnover triggered by PDGF at a concentration which did not produce maximal response. The increase of inositol phosphate metabolism produced by 20% serum was also unaffected by heparin. This concentration of serum elicited a response comparable to that induced by a submaximal concentration of PDGF.
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PMID:Binding and growth-inhibitory effect of heparin and oligo-heparin (2kDa) in Balb/c 3T3 cells: lack of effect on PDGF- or serum-induced inositol lipid turnover. 781 18

Matrix production by smooth muscle cells (SMC) appears to play a major role in the intimal thickening process. Proteoglycans (PG) are the predominant extracellular matrix component of early restenotic lesions. As angiotensin II (A II) has been proposed as a mediator of restenotic process, we hypothesized that A II may directly affect PG synthesis by SMC. SMC were cultured in the presence of [35S]sulfate and angiotensin II, and both the secreted and membrane-bound proteoglycans were analyzed. A II (1 to 100 nM) evoked a dose- and time-dependent increase in both cell- and media-associated PG production, an effect abrogated by the A II receptor antagonist, saralasin. SMC constitutively synthesize small amounts of PG with a molecular mass of 170-250 kDa. After treatment with A II, the abundance of PG is increased, as well as its molecular mass (230-300 kDa). Selective degradation by chondroitinases and heparinase identified chondroitin and dermatan sulfate PG as the predominant form being induced. These results demonstrate that the effect of A II is not general and is specific to certain classes of PGs. In order to further examine the specificity of the A II effect, we compared the synthesis of PG induced by A II with that induced by platelet-derived growth factors AA and BB (PDGF-AA and -BB), insulin-like growth factor I (IGF-I), and tumor necrosis factor alpha (TNF alpha). This comparison demonstrated that the profile of PG induced by A II is different from the other factors examined. Taken together, these data indicate that A II may not only function as a hypertrophic factor for SMC, but in addition may also be a potent modulator of specific PG synthesis by these same cells, which could significantly contribute to the formation of atherosclerotic and restenotic lesions.
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PMID:Stimulation of rat vascular smooth muscle cell glycosaminoglycan production by angiotensin II. 784 Aug 14

Heparinase III degrades heparan sulfate proteoglycans, which are co-receptors for growth factors that stimulate arterial proliferation. We assessed the ability of locally-delivered heparinase III to limit medial vascular smooth muscle cell proliferation induced by balloon catheter injury in rat carotid arteries. Whereas vehicle-treated arteries showed 12% of smooth muscle cells proliferating after 2 days, heparinase III (0.022-5.7 mg/kg) treated arteries showed 0.8-4%. Chemically-inactivated heparinase III did not limit proliferation. In isolated rat A10 vascular smooth muscle cells, heparinase III (1 IU/ml) inhibited both PDGF-BB and bFGF mediated increases in proliferation and migration. These results suggest that heparinase III can limit proliferation by affecting heparan sulfate proteoglycan binding growth factors following arterial injury.
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PMID:Heparinase III limits rat arterial smooth muscle cell proliferation in vitro and in vivo. 969 8