Antithrombin: An anticoagulant, anti‐inflammatory and antibacterial serpin

Rezaie, Alireza R.; Giri, Hemant

doi:10.1111/jth.14724

Cited by 17 publications

(16 citation statements)

References 45 publications

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“…Thus, β‐AT has been hypothesized to have therapeutic utility as an antimicrobial drug in infectious disease settings, 50 in particular in patients with sepsis where both coagulation and inflammatory pathways are highly upregulated. This question requires further investigation 56 …”

Section: Antibacterial and Antiviral Effects Of Atmentioning

confidence: 99%

“…48,54 Further investigation will also be required to determine whether this mechanism of AT-mediated CD13 and CD300f signaling is unique for monocytes or if it can occur in ECs. 50,56…”

Section: Anti -Infl Ammatory S Ig Naling Fun C Ti On Of Atmentioning

confidence: 99%

“…This question requires further investigation. 56 Similar to bacterial infection, viral infection has also been found to be associated with decreased AT levels and increased thrombosis. 80 HSPGs with lactoferrin was shown to inhibit binding of SARS-CoV on HEK-293E cells overexpressing ACE2 receptor.…”

Section: Antibac Terial and Antivir Al Effec Ts Of Atmentioning

confidence: 99%

“…Thus, further studies will be required to understand whether these receptors, similar to Synd‐4, contain high‐affinity AT‐binding GAGs that transmit signaling function of AT in monocytes 48,54 . Further investigation will also be required to determine whether this mechanism of AT‐mediated CD13 and CD300f signaling is unique for monocytes or if it can occur in ECs 50,56 …”

Section: Anti‐inflammatory Signaling Function Of Atmentioning

confidence: 99%

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Anticoagulant and signaling functions of antithrombin

Rezaie

Giri

2020

Journal of Thrombosis and Haemostasis

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Antithrombin (AT, also called AT III) is a serine protease inhibitor of the serpin superfamily that regulates the proteolytic activity of procoagulant proteases of both intrinsic and extrinsic pathways. 1-4 It is synthesized in the liver as a single-chain glycoprotein with 432 amino acids, three disulfide bonds, and four potential glycosylation sites. 5,6 It circulates in plasma with a concentration of 0.125 mg/ mL (~2.5 µmol/L), and its major form in the circulation is referred to as α-AT and carries carbohydrates at all four glycosylation sites. However, there is a minor fraction (5%-10%) that does not have the carbohydrate chain at Asn-135 and is referred to as β-AT. 7-9 The initial x-ray crystal structure of AT in the dimeric form with an

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Section: Antibacterial and Antiviral Effects Of Atmentioning

confidence: 99%

“…48,54 Further investigation will also be required to determine whether this mechanism of AT-mediated CD13 and CD300f signaling is unique for monocytes or if it can occur in ECs. 50,56…”

Section: Anti -Infl Ammatory S Ig Naling Fun C Ti On Of Atmentioning

confidence: 99%

Section: Antibac Terial and Antivir Al Effec Ts Of Atmentioning

confidence: 99%

Section: Anti‐inflammatory Signaling Function Of Atmentioning

confidence: 99%

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Anticoagulant and signaling functions of antithrombin

Rezaie

Giri

2020

Journal of Thrombosis and Haemostasis

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“…Furthermore, the β-isoform of antithrombin binds preferentially to vascular heparin sulfate proteoglycans and initiates prostacyclin production and inhibition of nuclear factor kappa B (NF-κB), resulting in anti-inflammatory effects, which might be further pronounced by the binding of β-antithrombin to receptors on monocytes. 120 Limited supporting data exist from patients with severe acute respiratory syndrome (SARS). Compared with healthy individuals such patients had lower levels of the natural inhibitors of coagulation and higher levels of PAI-1.…”

Section: Antithrombinmentioning

confidence: 99%

Pharmacological Agents Targeting Thromboinflammation in COVID-19: Review and Implications for Future Research

et al. 2020

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AbstractCoronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease. In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis. Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated. Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19. Further, we review other agents, including immunomodulators, that may have antithrombotic properties. It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.

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