Homocysteine inhibits neoangiogenesis in mice through blockade of annexin A2–dependent fibrinolysis

Annexin II regulates fibrin homeostasis and neoangiogenesis in vivo.

A central tenet of fibrinolysis is that tissue plasminogen activator-dependent (t-PA- dependent) conversion of plasminogen to active plasmin requires the presence of the cofactor/substrate fibrin. However, previous in vitro studies have suggested that the endothelial cell surface protein annexin II can stimulate t-PA-mediated plasminogen activation in the complete absence of fibrin. Here, homoz...

Homocysteine inhibits angiogenesis through cytoskeleton remodeling

Homocysteine (Hcy) is an intermediate non-diet amino acid connecting methionine and folate cycles. Elevated total Hcy level in blood, denoted as hyperhomocysteinemia, has emerged as a prevalent and strong risk factor for multiple diseases including atherosclerotic vascular disease in coronary, cerebral, and peripheral vessels. Its detrimental effect on vascular system implies the potential appl...

The endothelial cell annexin A2 system and vascular fibrinolysis.

Vascular endothelial cell surface expression of annexin A2 and its binding partner p11 is a key element in maintaining fibrinolytic balance on blood vessel surfaces. In the recent decade, investigators have made significant progress toward understanding the mechanisms that regulate heterotetrameric (A2*p11)(2) receptor translocation from the cytoplasm to the outer cell surface. Accumulating evi...

Factor V Inhibits Fibrinolysis In Vivo

Background—Factor V (fV) predisposes to thrombosis by enhancing thrombin formation. This study tested the hypothesis that fV inhibits fibrinolysis in vivo. Methods and Results—Radiolabeled clots were injected into the jugular veins of wild-type mice and mice heterozygous (fV ) or homozygous (fV) for fV. Mean percent clot lysis 5 hours later was significantly reduced in fV mice (14.3 3.6%, n 13)...

The role of the annexin A2 heterotetramer (AIIt) in vascular fibrinolysis Running title: S100A10 regulates vascular fibrinolysis