Disease relevance of Serpind1

• In this study, we estimated the antithrombotic effect of heparin cofactor II administered exogenously in a rat model of thrombosis [1].
• Effects of dermatan sulfate, a heparin cofactor II mediated thrombin inhibitor, on the endotoxin-induced disseminated intravascular coagulation model in the rat: comparison with low-molecular weight heparin, nafamostat mesilate and argathroban [2].

High impact information on Serpind1

• Deposition of the fibrin matrix in hepatocyte cultures was arrested by hirudin, by specific heparin oligosaccharides that potentiate thrombin inhibition by antithrombin III, and by dermatan sulfate, an activator of heparin cofactor II-mediated inhibition of thrombin [3].
• When the relative efficiency of cellular endocytosis of thrombin in complex with a number of inhibitors was examined, 125I-thrombin-PAI-1 complexes were most efficiently cleared compared to 125I-thrombin in complex with the serpins ATIII, HCII, alpha1-proteinase inhibitor, or d-phenylalanyl-l-prolyl-l-arginine chloromethyl ketone [4].
• Like heparin, they enhance thrombin and factor Xa inhibition by antithrombin and/or heparin cofactor II [5].
• An invertebrate dermatan sulfate containing 2-O-sulfated alpha-L-iduronic acid and 4-O-sulfated N-acetyl-beta-D-galactosamine residues is a potent anticoagulant due to a high heparin cofactor II activity [6].
• It inhibits thrombin due to the formation of a covalent complex with heparin cofactor II, as in the case of mammalian dermatan sulfate, but the effect occurs at lower concentrations for the invertebrate polysaccharide [6].

Biological context of Serpind1

• In the lateral crista, the maximum percentage of labeled HCI occurs on the 17th and 18th day of gestation and on the 19th day of gestation for the HCII [7].
• The location in time and space of the terminal mitoses of type I and type II sensory hair cells (HCI and HCII) of the developing crista ampullaris in rat lateral semicircular canal and macula utriculi was determined by radioautographs of specimens exposed to tritiated thymidine from the 13th to the 20th day of gestation [7].
• At an effective dose in this thrombosis model, heparin cofactor II did not prolong the activated partial thromboplastin time and the prothrombin time in normal rats [1].

Anatomical context of Serpind1

• Pretreatment with heparin cofactor II significantly prolonged the time required to occlude the femoral artery (occlusion time) in a dose-dependent manner [1].
• These results suggest that the administration of heparin cofactor II in vivo effectively inhibited thrombus formation on the vessel walls whose endothelium is damaged without a prolongation of the coagulation time while heparin cofactor II may also inhibit the thrombin activity in the subendothelial tissue in vivo [1].

Associations of Serpind1 with chemical compounds

• These results support the hypothesis that the heparin-binding sites of glia-derived nexin, antithrombin III, and heparin cofactor II are found in homologous regions of the molecules [8].
• These results show that the antithrombotic activity of naroparcil is dependent on modification in the plasma GAG profile which inactivates thrombin via the HCII [9].
• Agents are formulated with the anionic glycosaminoglycan, 435-type dermatan sulfate (DS 435, 22.2 kDa), chemically enriched for oligosaccharide sequences that confer high heparin cofactor II binding and correlate with high tumor uptake [10].
• The anticoagulant and possibly the antithrombotic actions of fucosylated chondroitin sulfate are mostly dependent on heparin cofactor II activity, and both are markedly reduced with the decrease of the chain size of the polymer [11].
• 1. Vestibular putative neurotransmitters GABA and acetylcholine synthesizing enzymes were quantified in four vertebrate species to find a correlation between all-vertebrate vestibular hair cell II (HCII) and synaptic contacts and appearance of hair cell I (HCI) and related synapses in terrestrial species [12].

Other interactions of Serpind1

• The results of these experiments indicated that the in vitro abilities of oversulfated fucoidan to stimulate tissue plasminogen activator (t-PA)-catalyzed plasminogen activation and to potentiate thrombin inhibition by antithrombin III or heparin cofactor II decreased with a decrease in its molecular size [13].

Analytical, diagnostic and therapeutic context of Serpind1

• In addition, the fractionation of the plasma GAG extract by affinity chromatography on immobilized HCII led to a more potent material whereas the low-affinity fraction was shown to be inactive in thrombin inhibition by HCII [9].
• In vitro bioassay showed maximum anti-Xa activity in the 4.2 kDa fraction and maximum heparin cofactor II-mediated anti-IIa activity in the 5.5 kDa fraction [14].

References