Venous stasis-induced fibrinolysis prevents thrombosis in mice: role of α2-antiplasmin

Singh, Satish; Houng, Aiilyan K.; Reed, Guy L.

doi:10.1182/blood.2019000049

Cited by 28 publications

(39 citation statements)

References 36 publications

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“…( http://www.nhlbi.nih.gov/health/dci/Diseases/pe/pe_what.html ). (3) In arterial (carotid artery injury) and venous (IVC, jugular vein) injury/thrombosis models, α2AP increases thrombosis and decreases fibrinolysis ( 63 , 64 ). α2AP is also associated with increased neointima formation and reduced endothelialization over time ( 65 ).…”

Section: Role Of α2ap In Animal Models Of Cardiovascular and Cerebrovmentioning

confidence: 99%

“…Since its discovery, the effects of α2AP were considered to be restricted to inhibiting the dissolution of formed thrombi; it was not thought to have a role in regulating thrombus formation or thrombosis ( 70 ). However, new data show that α2AP regulates thrombus initiation and thrombus development, and is required for the occurrence of stasis induced deep vein thrombosis in mice ( 64 ) ( Figure 2 ). In mice with normal levels of α2AP, thrombosis induces plasmin generation ( 64 ), however thrombosis proceeds because the plasmin generated, is insufficient to overcome the anti-fibrinolytic effects of α2AP.…”

Section: Role Of α2ap In Animal Models Of Cardiovascular and Cerebrovmentioning

confidence: 99%

“…However, new data show that α2AP regulates thrombus initiation and thrombus development, and is required for the occurrence of stasis induced deep vein thrombosis in mice ( 64 ) ( Figure 2 ). In mice with normal levels of α2AP, thrombosis induces plasmin generation ( 64 ), however thrombosis proceeds because the plasmin generated, is insufficient to overcome the anti-fibrinolytic effects of α2AP. In contrast, in α2AP deficiency, plasmin-driven fibrinolysis prevents the initiation and establishment of thrombosis.…”

Section: Role Of α2ap In Animal Models Of Cardiovascular and Cerebrovmentioning

confidence: 99%

“…In contrast, in α2AP deficiency, plasmin-driven fibrinolysis prevents the initiation and establishment of thrombosis. Indeed, in venous thrombosis induced by stasis (no blood flow), or by stenosis (reduced flow), α2AP −/− mice do not develop thrombosis even after hours to weeks ( 64 ). The requirement for α2AP to enable the development of thrombosis appears to be mediated through its inhibition of plasmin because another plasmin inhibitor, ε-aminocaproic acid ( 64 ) will restore thrombus formation in the absence of α2AP.…”

Section: Role Of α2ap In Animal Models Of Cardiovascular and Cerebrovmentioning

confidence: 99%

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Alpha2-Antiplasmin: The Devil You Don't Know in Cerebrovascular and Cardiovascular Disease

Singh

Saleem

Reed

2020

Front. Cardiovasc. Med.

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Alpha2-antiplasmin (α2AP), the fast-reacting, serine protease inhibitor (serpin) of plasmin, was originally thought to play a key role in protection against uncontrolled, plasmin-mediated proteolysis of coagulation factors and other molecules. However, studies of humans and mice with genetic deficiency of α2AP have expanded our understanding of this serpin, particularly in disease states. Epidemiology studies have shown an association between high α2AP levels and increased risk or poor outcome in cardiovascular diseases. Mechanistic studies in disease models indicate that α2AP stops the body's own fibrinolytic system from dissolving pathologic thrombi that cause venous thrombosis, pulmonary embolism, arterial thrombosis, and ischemic stroke. In addition, α2AP fosters the development of microvascular thrombosis and enhances matrix metalloproteinase-9 expression. Through these mechanisms and others, α2AP contributes to brain injury, hemorrhage and swelling in experimental ischemic stroke. Recent studies also show that α2AP is required for the development of stasis thrombosis by inhibiting the early activation of effective fibrinolysis. In this review, we will discuss the key role played by α2AP in controlling thrombosis and fibrinolysis and, we will consider its potential value as a therapeutic target in cardiovascular diseases and ischemic stroke.

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Section: Role Of α2ap In Animal Models Of Cardiovascular and Cerebrovmentioning

confidence: 99%

Section: Role Of α2ap In Animal Models Of Cardiovascular and Cerebrovmentioning

confidence: 99%

Section: Role Of α2ap In Animal Models Of Cardiovascular and Cerebrovmentioning

confidence: 99%

Section: Role Of α2ap In Animal Models Of Cardiovascular and Cerebrovmentioning

confidence: 99%

See 2 more Smart Citations

Alpha2-Antiplasmin: The Devil You Don't Know in Cerebrovascular and Cardiovascular Disease

Singh

Saleem

Reed

2020

Front. Cardiovasc. Med.

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“…Although the role of venous stasis was accepted, the link between stasis and thrombosis for example after a long flight or immobilization remained for long time elusive [4][5][6]. A reduction of the fibrinolytic capacity is conceivable [7] but evidence in the human model is lacking [8]. The interactions between coagulation and other humoral systems such as complement [9] and immune system [10] are ongoing and complex.…”

Section: Introductionmentioning

confidence: 99%

Thrombophilia screening revisited: an issue of personalized medicine

Colucci

Tsakiris

2020

J Thromb Thrombolysis

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Clinical thrombophilia is the consequence of multiple gene and/or environment interactions. Thrombophilia screening requires a targeted patient with specific indication, in which a finding would have implications. Carrying out a thrombophilia examination in the physician's practice is often a cause of uncertainty and concern. The concerns begin in choosing the right patient to be examined, are associated with the time of investigation, with the choice of analysis, the test-material and with the correct interpretation of the results. Difficulties, which can influence the results, can occur with both organization and blood sampling. As common for any analysis, pre-analytical, analytical and post-analytical factors should be considered, as well as the possibility of false positive or false negative results. Finally, recommendation of correct therapeutic and prophylactic measures for the patient and his relatives is an additional focus. In this article we want to provide-on the basis of the evidence and personal experience-the theory of thrombophilia-investigation, the indications for testing, as well as practical recommendations for treatment options. Keywords Venous thromboembolism • Thrombophilia screening • Genetic thrombophilia Highlights • Thrombophilia screening should be a global, comprehensive, personalized evaluation of the patient's prothrombotic state. • Global thrombophilia evaluation is indicated in all patients with thromboembolism, whereas thrombophiliaspecific laboratory screening only in selected cases. • Thrombophilia investigation should not be performed just for defining the duration of anticoagulation, but it helps in estimating the individual recurrence risk for throm-botic disease, the need for thrombotic prophylaxis or for the decision to prolong anticoagulation therapy. • Genetic causes of thrombophilia are significant risk factors for a first thromboembolic event but they do not influence decisively recurrent thrombotic risk. • Although single genetic thrombophilia is mostly kept in balance in children and young adults, it can cause serious thrombotic disease in adults, as soon as acquired risk factors are additionally prevalent (gene-environment interaction) or if multiple deviations in thrombophilia genes co-exist (gene-gene interaction). Dedicato a mio padre Vincenzo, esempio perenne di onestà e bontà umana (06.02.1944-22.03.2020).

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The effect of resting and compression time post-centrifugation on the characteristics of platelet rich fibrin (PRF) membranes

et al. 2022

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Venous stasis-induced fibrinolysis prevents thrombosis in mice: role of α2-antiplasmin

Cited by 28 publications

References 36 publications

Alpha2-Antiplasmin: The Devil You Don't Know in Cerebrovascular and Cardiovascular Disease

Alpha2-Antiplasmin: The Devil You Don't Know in Cerebrovascular and Cardiovascular Disease

Thrombophilia screening revisited: an issue of personalized medicine

The effect of resting and compression time post-centrifugation on the characteristics of platelet rich fibrin (PRF) membranes

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