2021
DOI: 10.3389/fcvm.2020.622778
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Serpins in Hemostasis as Therapeutic Targets for Bleeding or Thrombotic Disorders

Abstract: Bleeding and thrombotic disorders result from imbalances in coagulation or fibrinolysis, respectively. Inhibitors from the serine protease inhibitor (serpin) family have a key role in regulating these physiological events, and thus stand out as potential therapeutic targets for modulating fibrin clot formation or dismantling. Here, we review the diversity of serpin-targeting strategies in the area of hemostasis, and detail the suggested use of modified serpins and serpin inhibitors (ranging from small-molecule… Show more

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Cited by 11 publications
(8 citation statements)
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References 52 publications
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“…An increased expression in injured tissues of swine 2 and swine 3 after EMF application suggests the beneficial role of EMF in promoting oligodendrocyte proliferation and myelination, both required for the repair of the injured tissue. SERPINE 1 (serine proteinase inhibitor (serpin) family E member 1) encoding for protein plasminogen activator inhibitor 1 (PAI-1) is involved in hemostasis (normal blood clotting) after an injury as a powerful procoagulant by inhibiting tPA/uPA, thrombomodulin, and activated protein C [ 19 , 20 ]. PAI-1 also regulates immune cell infiltration [ 21 ].…”
Section: Resultsmentioning
confidence: 99%
“…An increased expression in injured tissues of swine 2 and swine 3 after EMF application suggests the beneficial role of EMF in promoting oligodendrocyte proliferation and myelination, both required for the repair of the injured tissue. SERPINE 1 (serine proteinase inhibitor (serpin) family E member 1) encoding for protein plasminogen activator inhibitor 1 (PAI-1) is involved in hemostasis (normal blood clotting) after an injury as a powerful procoagulant by inhibiting tPA/uPA, thrombomodulin, and activated protein C [ 19 , 20 ]. PAI-1 also regulates immune cell infiltration [ 21 ].…”
Section: Resultsmentioning
confidence: 99%
“…Sometimes the homeostatic process is not able to recover, and a pathological condition is generated. For this reason, in the literature, many papers that try to explain this mechanism have been published; however, for historical and cultural reasons, most of these articles are clinical and therefore explain how homeostasis is implemented at the cellular level (see, e.g., [35][36][37]). On the other hand, in the last twenty years, there has also been an increasing number of papers that try to describe the mechanism through mathematical models (see, among others, [32,[38][39][40][62][63][64]).…”
Section: Discussionmentioning
confidence: 99%
“…The proposed model is composed of a set of two nonlinear ordinary differential equations (ODEs), where each term of the equations has a well-defined function in the feedback mechanism underlying the physiological process and a precise mathematical characterisation. It is well-known that many papers, dealing with the modelling of physiological systems, have been published in the literature [32,[35][36][37][38][39][40]. However, they have some drawbacks, such as, for example, to investigate only the anatomical issues; hence, they can only describe specific cases.…”
Section: Introductionmentioning
confidence: 99%
“…Many serpin E2 functions are related to its inhibitory effect on plasminogen activator (PA), including regulation of hemostasis, cell adhesion, and promotion of tumor metastasis ( Czekay and Loskutoff, 2009 ; Bharadwaj et al, 2021 ; Bianchini et al, 2021 ). There are two types of PA in humans: uPA and tPA ( Danø et al, 1985 ; Vassalli et al, 1991 ).…”
Section: Serpin E2 Expression and Structurementioning
confidence: 99%