Inhibition of thromboxane A2 synthesis in human platelets by coagulation factor Xa.

Sinha, Asru K.; Rao, A Koneti; Willis, J; Colman, Robert W.

doi:10.1073/pnas.80.19.6086

Cited by 24 publications

(20 citation statements)

References 21 publications

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“…10 " 13 We have recently demonstrated 22 that this important procoagulant enzyme is also a potent inhibitor of thromboxane Aj synthesis in platelets. We show in the present study that this coagulation factor also has an inhibitory effect on the synthesis of a major prostanoid in endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…Purified platelet calcium-activated cysteine protease also inhibits PGI 2 synthesis in endothelial cells. 27 We have shown previously 22 that Factor Xa inhibits thromboxane A;, (TXA^ synthesis in platelets. The present study indicates that this procoagulant also may control the PGI 2 synthesis in endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…The details of the preparation of Factor Xa have been reported before. 22 Diisopropyl fluorophosphate (iPr 2 -F) inactivated Factor Xa (iPr 2 -Xa) was prepared by this method, 22 and 6[5, 8, 9,11, 12, 14, 15-3 H(N)], keto-PGF la (specific activity, 120 Ci/mmol) was obtained from New England Nuclear, Boston, Massachusetts. All other chemicals were analytical grade.…”

Section: Methodsmentioning

confidence: 99%

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Coagulant factor Xa inhibits prostacyclin formation in human endothelial cells. Role of factor V.

Sinha¹,

Duttaroy²,

Chiu³

et al. 1985

Arteriosclerosis

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Thrombin stimulates prostacyclin formation in cultured human endothelial cells. However, a countervailing process that prevents prostacyclin overproduction has not been described previously. In this study, we demonstrate that Factor Xa can inhibit prostacyclin synthesis induced by thrombin or sodium arachidonate. The required concentration of Factor Xa represents activation of only 2% of the Factor X in plasma. The inhibition is reversed by a human monoclonal antibody directed against the light chain of Factor Va (Mr = 78,000), which suggests that Factor Va is required for this down-regulation of prostacyclin production. Confluent human endothelial cells (10(7)) contained 1.4 to 2.2 micrograms of Factor V antigen as measured by a competitive enzyme-linked immunosorbent assay. The results indicate that in endothelial cells Factor Xa may play a regulatory role in prostacyclin formation through interaction with Factor Va.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Coagulant factor Xa inhibits prostacyclin formation in human endothelial cells. Role of factor V.

Sinha¹,

Duttaroy²,

Chiu³

et al. 1985

Arteriosclerosis

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“…Factor V has a dual function in procoagulation and anticoagulation pathways (47). In individuals with SCI, after the eighth session of FES-LCE exercise training, Factor V activity increased significantly, acting as a cofactor to reduce Factor VIII activity and thrombin generation.…”

Section: Discussionmentioning

confidence: 99%

Lower-Extremity Functional Electrical Stimulation Decreases Platelet Aggregation and Blood Coagulation in Persons With Chronic Spinal Cord Injury: A Pilot Study

Kahn

Feldman

Bauman

2010

The Journal of Spinal Cord Medicine

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Background: Individuals with spinal cord injury (SCI) develop premature cardiovascular disease. Regular exercise reduces the incidence and symptoms of cardiovascular disease in able-bodied individuals; these salutary effects of exercise have not been documented in persons with SCI. Objective: To evaluate the effects of functional electrical stimulation leg cycle ergometry (FES-LCE) exercise training on platelet aggregation and blood coagulation in persons with SCI. Participants: Subjects (n 5 14) with stable chronic (.1 year) paraplegia (T1-T10) or tetraplegia (C4-C8). Methods: Blood samples were collected before and after the first and eighth sessions (2 sessions per week for 4 weeks) of FES exercise. Results: Platelet aggregation was inhibited by 20% after the first session and by 40% (P , 0.001) after the eighth session. Thrombin activity was unchanged after the first session (10.7 ± 0.85 s to 10.43 ± 0.56 s) and decreased after the eighth session (12.5 ± 1.98 s to 11.1 ± 1.7 s; P , 0.0003). Antithrombin III activity increased after the first (103.8% ± 8.9% to 110% ± 6.9%; P , 0.0008) and eighth sessions (107.8% ± 12.1% to 120.4% ± 13.1%; P , 0.0001). Cyclic adenosine monophosphate increased after the first (9.9% ± 2.5% to 15.8% ± 3%; P , 0.001) and eighth sessions (17.8% ± 4.2% to 36.5% ± 7.6%; P , 0.0001). After the eighth session, factors V and X increased significantly (88% ± 27% to 103% ± 23%, P , 0.0001; 100% ± 40% to 105% ± 7%, P , 0.01, respectively); factors VII and VIII and fibrinogen did not change significantly. A significant reduction in platelet activation/aggregation was demonstrated in response to FES-LCE. The decrease in thrombin level was caused by the simultaneous increase in antithrombin activity. Conclusion: These findings provide new insight into the potential protective effects of FES-LCE against the risk of cardiovascular disease.

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“…[17][18][19][20] Aggregation of platelets by these agonists is mediated, in part, through the intracellular synthesis of PGG 2 and TXA2. 17 Platelet aggregation is inhibited by several autacoids, including prostanoids, such as PGI 2 , and PGE 1 or PGD 2 ; 18 blood coagulation factor Xa; 20 and endothelium-derived relaxing factor/nitric oxide.…”

Section: Platelets As Sources Of Active Componentsmentioning

confidence: 99%

Non-conventional hemostatic risk factors for coronary heart disease in individuals with spinal cord injury

et al. 2011

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Study design: Review. Objectives: In subjects with spinal cord injury (SCI), there is strong evidence for platelet hyperactivity, which may stimulate atherosclerosis and coronary heart disease (CHD). The literature was reviewed. Background: Individuals with SCI develop premature CHD. In addition to the conventional risk factors associated with CHD, there are pathologic hematological factors involved in atherogenesis that are similar to those that have been demonstrated in individuals with diabetes, and these hematological factors might affect individuals with SCI. One such hematological factor, platelet aggregation, is essential for the development of CHD, which results from thrombus formation in the coronary vasculature. Prostacyclin (PGI 2 ) is a potent inhibitor of platelet aggregation and is thought to have a beneficial role in inhibiting atherogenesis; therefore, it is possible that individuals with SCI have impaired PGI 2 receptor function. Methods: We reviewed the literature by conducting a search using PubMed (1970PubMed ( -2007. Results: Acute thrombosis is emerging as an important factor in the etiology of CHD and therefore could mediate the risk of CHD in persons with SCI, in addition to previously known risk factors such as hyperlipidemia, hypertension, hyperlipidemia, diabetes mellitus and hyperinsulinemia. Because PGI 2 may retard atherogenesis through its inhibitory effects on platelet function, we discuss the effects of PGI 2 on platelets in persons with SCI in this review. Conclusions Subjects with chronic SCI develop abnormal platelet function, resulting in the production of atherogenic and thrombogenic factors for the following reasons: (1) the PGI 2 and insulin receptors on their platelets are impaired; (2) thrombin generation and platelet-derived growth factor release are elevated; (3) insulin-induced nitric oxide production by platelets is markedly impaired; and (4) a circulating antibody (immunoglobulin G (IgG)) blocks the antithrombotic effect of both insulin and PGI 2 receptors. Thus, this IgG molecule is thought to be one of the pathological mediators of the increased incidence of CHD in individuals with SCI.

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Inhibition of thromboxane A2 synthesis in human platelets by coagulation factor Xa.

Cited by 24 publications

References 21 publications

Coagulant factor Xa inhibits prostacyclin formation in human endothelial cells. Role of factor V.

Coagulant factor Xa inhibits prostacyclin formation in human endothelial cells. Role of factor V.

Lower-Extremity Functional Electrical Stimulation Decreases Platelet Aggregation and Blood Coagulation in Persons With Chronic Spinal Cord Injury: A Pilot Study

Non-conventional hemostatic risk factors for coronary heart disease in individuals with spinal cord injury

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