biostudies-literatureUnknown9(5)Biswas I<h4>Abstract</h4>Antithrombin (AT) is an anticoagulant serpin involved in the regulation of proteolytic activities of coagulation proteases. AT also possesses a direct anti-inflammatory function. The anticoagulant function of AT is mediated through its reactive center loop-dependent inhibition of coagulation proteases, but anti-inflammatory function of AT is mediated via its D-helix-dependent interaction with vascular glycosaminoglycans (GAGs). In vitro assays have established that therapeutic heparins promote the anticoagulant function of AT by binding D-helix and activating the serpin, however, the contribution of vascular GAGs to D-helix-dependent anticoagulant function of AT has remained poorly understood in vivo. Here, we explored this question by using 2 AT mutants, (AT-4Mut), which Blood advances966-978https://www.ebi.ac.uk/biostudies/studies/S-EPMC11907474biostudies-literaturePhysiological significance of antithrombin D-helix interaction with vascular GAGs.PMC11907474Lupu FBiswas IRezaie ARPanicker SRfalsePhysiological significance of antithrombin D-helix interaction with vascular GAGs.<h4>Abstract</h4>Antithrombin (AT) is an anticoagulant serpin involved in the regulation of proteolytic activities of coagulation proteases. AT also possesses a direct anti-inflammatory function. The anticoagulant function of AT is mediated through its reactive center loop-dependent inhibition of coagulation proteases, but anti-inflammatory function of AT is mediated via its D-helix-dependent interaction with vascular glycosaminoglycans (GAGs). In vitro assays have established that therapeutic heparins promote the anticoagulant function of AT by binding D-helix and activating the serpin, however, the contribution of vascular GAGs to D-helix-dependent anticoagulant function of AT has remained poorly understood in vivo. Here, we explored this question by using 2 AT mutants, (AT-4Mut), which 2025-01-01T00:00:00Z2025 Mar2025-04-05T22:06:03.221Z2025-04-05T22:06:03.221ZS-EPMC119074743967130010.1182/bloodadvances.2024014756