Thrombospondin-1 and ADAMTS13 competitively bind to VWF A2 and A3 domains in vitro

Wang, Anyou; Liu, Fang; Dong, Ningzheng; Ma, Zhengliang; Zhang, Jingyu; Su, Jian; Zhao, Yiming; Ruan, Changgeng

doi:10.1016/j.thromres.2010.07.009

Cited by 44 publications

(51 citation statements)

References 19 publications

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“…However, the evidence to support the role of TSP1 in platelet adhesion to the injured vessel wall is not well elucidated and remains debatable. Previous studies under static or flow conditions have shown that TSP1 has both adhesive and antiadhesive properties, depending on the presence or absence of Ca 21 ions, respectively. 30,39,40 Agbanyo et al, 30 suggested that adhesive function of TSP1 depended on its conformation (requires Ca 21 ions) and is maximal at higher arterial shear rate.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, in vitro studies suggested that TSP1 and recombinant ADAMTS13 compete for binding to recombinant VWF A2 and A3 domain. 21,22 On the other hand, TSP1 has also been suggested to act as a reductase that controls VWF multimer size, and thereby may negatively regulate thrombus growth. 22,23 Second, TSP1 could directly interact with its counter receptors on platelets, particularly CD36, 20 to mediate platelet adhesion under arterial shear and thereby promote thrombosis.…”

Section: Discussionmentioning

confidence: 99%

“…22 The K d for soluble TSP1 binding to VWF A2 domain is not known, but we speculate that it could be similar (;3 mM) to A3 domain because in the residual collagen binding assay it was shown that TSP1 (100 nM) competes with both VWF A2 and A3 domain to a similar extent. 21 On the other hand, the levels of ADAMTS13 in plasma is ;1000 ng/mL (;7 nM), 44 and has much higher affinity for VWF (K d ; 15 nM). 45 Together, these observations suggest that it is highly unlikely that low TSP1 (;400-500 pM) present at basal levels in plasma could compete with ADAMTS13 (;7 nM) for VWF A2 and A3 binding.…”

Section: Discussionmentioning

confidence: 99%

“…43,46 At these concentrations, TSP1 has been shown to cause significant (;50%) inhibition of ADAMTS13 activity. 21 Based on these reports, we hypothesized that higher concentrations of TSP1 released from activated platelets within thrombus milieu modulate thrombus growth by preventing cleavage of VWF by ADAMTS13. To test this hypothesis, we depleted platelets in GPIba-hIL4R transgenic mice and reinfused them with either Tsp1 2/2 or WT platelets.…”

Section: Discussionmentioning

confidence: 99%

“…20 On the other hand, TSP1 has been shown to compete with ADAMTS13 for binding A2 and A3 domains of VWF, thus protecting it from proteolytic cleavage. 21 TSP1 has also been shown to regulate multimer size of circulating VWF, or VWF released from activated platelets. 22,23 Together, these studies suggest that TSP1 may modulate arterial thrombosis via VWF; however, definitive in vivo evidence to support this mechanism remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Thrombospondin 1 requires von Willebrand factor to modulate arterial thrombosis in mice

Prakash

Kulkarni

Chauhan

2015

Blood

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Thrombospondin 1 requires von Willebrand factor to modulate arterial thrombosis in mice

Prakash

Kulkarni

Chauhan

2015

Blood

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ADAMTS13 and von Willebrand factor assessment in steady state and acute vaso‐occlusive crisis of sickle cell disease

Demagny¹,

Driss²,

Stépanian³

et al. 2021

Research and Practice in Thrombosis and Haemostasis

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Background Sickle cell disease (SCD) is characterized by vaso‐occlusive crisis (VOC), acute chest syndrome (ACS) and multiorgan failure (MOF) complicated by thrombosis. Von Willebrand factor (VWF) is a strong marker of SCD‐related endothelial injury. Objectives To decipher the role of VWF and its specific‐cleaving metalloprotease, ADAMTS13, in the vaso‐occlusive and thrombotic process of SCD. Patients/Methods We investigated the VWF antigen (Ag), ADAMTS13 activity, ADAMTS13 Ag and ADAMTS13 IgGs in a cohort of 65 patients with SCD prospectively enrolled in a 20‐month period from three centers. Patients were divided into two groups: an asymptomatic group (n = 30) with treated or untreated SCD at steady state, and a VOC/ACS group (n = 35) with SCD with VOC/ACS requiring either medical management or intensive care management for MOF. Results and Conclusions VWF:Ag levels were increased (median, 167 IU/dL; interquartile range [IQR], 124 ‐ 279), especially in patients with VOC SCD (227 IU/dL; IQR, 134‐305; P = .04), and positively correlated with inflammatory markers ( P < .02). Median ADAMTS13 activity was normal (70 IU/dL; IQR, 60‐80), but 7 patients exhibited a partial deficiency between 25 and 45 IU/dL. ADAMTS13 activity/VWF:Ag ratio, however, did not change during VOC. Median ADAMTS13:Ag was slightly decreased (611 ng/mL; IQR, 504‐703) with no significant difference between groups. Surprisingly, ADAMTS13 IgGs were detected in 33 (51%) of our patients. We conclude that, in SCD, VWF:Ag and nonrelevant ADAMTS13 IgGs may reflect the severity of the inflammatory vasculopathy enhancing vaso‐occlusive and thrombotic complications.

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ADAMTS13 and its variants promote angiogenesis via upregulation of VEGF and VEGFR2

Lee

Keener

Xiao

et al. 2014

Cell. Mol. Life Sci.

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Severe plasma ADAMTS13 deficiency results in the clinical disorder thrombotic thrombocytopenic purpura. However, other potential pathophysiological roles of ADAMTS13 in endothelial cell biology remain unexplored. The goals of this study were to understand the angiogenic pathways ADAMTS13 activates and to identify the important structural components of ADAMTS13 that stimulate angiogenesis. Incubation of human umbilical vein endothelial cells (HUVEC) with 150 ng/mL (1 nM) of recombinant human ADAMTS13 induced VEGF expression by 53 % and increased VEGF mRNA by over sixfold, both within 10 min; the measured VEGF levels steadily decreased over 2 h, as shown by Western blot and ELISA. Phosphorylation of VEGFR2 was significantly enhanced in HUVEC after incubation with ADAMTS13 (1 nM). Structure-function analysis showed that an ADAMTS13 variant containing thrombospondin type 1 (TSP1) 2-8 repeats (TSP1 2-8), TSP1 2-8 plus CUB domains (TSP1 2-8 plus CUB), or TSP1 5-8 repeats plus CUB domains (TSP1 5-8 plus CUB) increased HUVEC proliferation by 41-54 % as compared to the EBM-2 controls. Chemotaxis assays further demonstrated that the TSP1 domains of ADAMTS13 increased HUVEC migration by 2.65-fold. Incubation of HUVEC with both ADAMTS13 variants containing TSP1 repeats and anti-VEGF IgG abrogated the enhanced effect of ADAMTS13 on proliferation, migration, and VEGFR2 phosphorylation. In conclusion, ADAMTS13-induced endothelial cell angiogenesis occurs via the upregulation of VEGF and phosphorylation of VEGFR2. This angiogenic activity depends on the C-terminal TSP1 repeats of ADAMTS13.

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Thrombospondin-1 and ADAMTS13 competitively bind to VWF A2 and A3 domains in vitro

Cited by 44 publications

References 19 publications

Thrombospondin 1 requires von Willebrand factor to modulate arterial thrombosis in mice

Thrombospondin 1 requires von Willebrand factor to modulate arterial thrombosis in mice

ADAMTS13 and von Willebrand factor assessment in steady state and acute vaso‐occlusive crisis of sickle cell disease

ADAMTS13 and its variants promote angiogenesis via upregulation of VEGF and VEGFR2

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