PURPOSE To evaluate the efficacy of recombinant adeno-associated virus (rAAV) vector expressing mouse angiostatin (Kringle domains 1 to 4) in reducing retinal vascular leakage in an experimental diabetic rat model. METHODS rAAV-angiostatin was delivered by intravitreal injection to the right eyes of Sprague-Dawley rats. As a control, the contralateral eye received an intravitreal injection of...

Jiang, Lianwei, Vivekanand Jha, Mohanraj Dhanabal, Vikas P. Sukhatme, and Seth L. Alper. Intracellular Ca21 signaling in endothelial cells by the angiogenesis inhibitors endostatin and angiostatin. Am J Physiol Cell Physiol 280: C1140–C1150, 2001.—Intracellular signaling mechanisms by the angiogenesis inhibitors endostatin and angiostatin remain poorly understood. We have found that endostatin ...

PURPOSE Antiangiogenic treatment is a promising new therapy for angiogenesis-dependent diseases. In the current study, the biologic effects on pathologic and physiological angiogenesis in the retina of angiostatin, a very potent angiogenesis inhibitor were determined. In addition, the effects of angiostatin on the growth and development of newborn mice were examined. METHODS Oxygen-induced re...

We previously showed that the kringle domains of plasmin and angiostatin, the N-terminal four kringles (K1-4) of plasminogen, directly bind to integrins. Angiostatin blocks tumor-mediated angiogenesis and has great therapeutic potential. Angiostatin binding to integrins may be related to the antiinflammatory action of angiostatin. We reported that plasmin induces signals through protease-activa...

OBJECTIVE We have previously shown that transient coronary artery occlusion stimulated coronary collateral growth (CCG) in healthy (Sprague Dawley) but not in metabolic syndrome (JCR:LA-cp [JCR] ) rats. Here, we sought to determine whether matrix metalloproteinases (MMPs) negatively regulate CCG in the metabolic syndrome via release of endostatin and angiostatin. APPROACH AND RESULTS Rats und...

Integrin alpha1beta1 is a collagen receptor abundantly expressed on microvascular endothelial cells. As well as being the only collagen receptor able to activate the Ras/Shc/mitogen-activated protein kinase pathway promoting fibroblast cell proliferation, it also acts to inhibit collagen and metalloproteinase (MMP) synthesis. We have observed that in integrin alpha1-null mice synthesis of MMP7 ...

Angiostatin is a plasminogen-derived anti-angiogenic factor composed of its first four kringle structures. This molecule is generated by proteolytic cleavage of plasminogen by some proteolytic enzymes in vitro. Since venoms of viper snakes are a rich source of both serine- and metalloproteinase, we hypothesized that angiostatin-like polypeptides could be generated during the envenomation after ...

Acute lung injury is marked by profound influx of activated neutrophils, which have delayed apoptosis, along with fluid accumulation that impairs lung function and causes high mortality. Inflammatory and antimicrobial molecules, such as reactive oxygen species from activated neutrophils with prolonged lifespan, cause tissue damage and contribute to lung dysfunction. Angiostatin, an endogenous a...

Human plasminogen-derived angiostatin is one of the most potent antiangiogenic agents currently known. However, it is unclear whether angiostatin is also effective against accelerated tumor growth induced by local up-regulation of growth factors, including angiogenesis stimulators, such as in regenerating liver. Prior to addressing this question, we tested, in mice, whether continuous administr...

To determine the mechanism responsible for the in vivo production of angiostatin that inhibits growth and metastasis in Lewis lung carcinoma (3LL), we implanted 3LL variant cells into the subcutis of syngeneic C57BL/6 mice. The tumors were infiltrated by macrophages and expressed high levels of steady-state mRNA for metalloelastase (MME). Successive passages (more than three) of cultures establ...