期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 124, 期 10, 页码 4281-4293出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI74630
关键词
-
资金
- Canadian Institutes of Health Research (CIHR) [MOP 119540]
- Heart and Stroke Foundation of Canada (Ontario)
- CIHR team grant in venous thromboembolism
- Canada Foundation for Innovation
- Canadian Blood Services
- St. Michael's Hospital
- Meredith and Malcolm Silver Scholarship in Cardiovascular Studies
Plasma fibronectin (pFn) has long been suspected to be involved in hemostasis; however, direct evidence has been lacking. Here, we demonstrated that pFn is vital to control bleeding in fibrinogen-deficient mice and in WT mice given anticoagulants. At the site of vessel injury, pFn was rapidly deposited and initiated hemostasis, even before platelet accumulation, which is considered the first wave of hemostasis. This pFn deposition was independent of fibrinogen, von Willebrand factor, 113 integrin, and platelets. Confocal and scanning electron microscopy revealed pFn integration into fibrin, which increased fibrin fiber diameter and enhanced the mechanical strength of clots, as determined by thromboelastography. Interestingly, pFn promoted platelet aggregation when linked with fibrin but inhibited this process when fibrin was absent. Therefore, pFn may gradually switch from supporting hemostasis to inhibiting thrombosis and vessel occlusion following the fibrin gradient that decreases farther from the injured endothelium. Our data indicate that pFn is a supportive factor in hemostasis, which is vital under both genetic and therapeutic conditions of coagulation deficiency. By interacting with fibrin and platelet beta 3 integrin, pFn plays a self-limiting regulatory role in thrombosis, suggesting pFn transfusion may be a potential therapy for bleeding disorders, particularly in association with anticoagulant therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据