HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Inhibition of tumor angiogenesis in vivo by a monoclonal antibody targeted to domain 5 of high molecular weight kininogen

HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY A monoclonal antibody against CD148, a receptor-like tyrosine phosphatase, inhibits endothelial-cell growth and angiogenesis

Angiogenesis contributes to a wide range of neoplastic, ischemic, and inflammatory disorders. Definition of the intrinsic molecular controls in angiogenic vessel growth promises novel therapeutic approaches for angiogenesis-related diseases. CD148 (also named DEP-1/PTP ) is a receptor-like protein tyrosine phosphatase that is abundantly expressed in vascular endothelial cells. To explore a role...

HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY A novel anti-CD146 monoclonal antibody, AA98, inhibits angiogenesis and tumor growth

Kininostatin, an angiogenic inhibitor, inhibits proliferation and induces apoptosis of human endothelial cells.

We recently reported that domain 5 (D5) of high-molecular-weight kininogen inhibited critical steps required for angiogenesis. Thus, it was named kininostatin. To understand its mechanism of action, we further investigated the effects of D5 on basic fibroblast growth factor (bFGF)-induced endothelial cell proliferation and cell viability. We report here that D5-inhibited cell proliferation of h...

High-molecular-weight kininogen fragments stimulate the secretion of cytokines and chemokines through uPAR, Mac-1, and gC1qR in monocytes.

OBJECTIVE Plasma high-molecular-weight kininogen (HK) is cleaved in inflammatory diseases by kallikrein to HKa with release of bradykinin (BK). We postulated a direct link between HKa and cytokine/chemokine release. METHODS AND RESULTS HKa, but not BK, releases cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and chemokines IL-8 and MCP-1 from isolated human mononucl...

HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Inhibition of the von Willebrand (VWF)–collagen interaction by an antihuman VWF monoclonal antibody results in abolition of in vivo arterial platelet thrombus formation in baboons

The interaction between collagen, von Willebrand factor (VWF), and glycoprotein Ib is the first step in hemostasis and thrombosis especially under high shear conditions. We studied the inhibition of the VWF-collagen interaction by using an antihuman VWF monoclonal antibody 82D6A3 to prevent arterial thrombosis in baboons to develop a new kind of antithrombotic strategy and determine for the fir...