STAT1 activation by venous malformations mutant Tie2-R849W antagonizes VEGF-A-mediated angiogenic response partly via reduced bFGF production.

A missense mutation from arginine to tryptophan at residue 849 in the kinase domain of Tie2 (Tie2-R849W) is commonly identified in familial venous malformations. The mechanistic action of Tie2-R849W variant expression on angiogenic cascades including smooth muscle cell recruitment, however, remains elusive. To avoid confounding factors from endogenous Tie2 expression, Tie2-depleted endothelial cells (ECs) were used to study the effects of ectopic shRNA-resistant Tie2 variant expression, Tie2-WT* and Tie2-R849W*, on vascular cell proliferation, migration, tube formation, and smooth muscle cell (SMC) recruitment.

Triptolide functions as a potent angiogenesis inhibitor.

Triptolide is a key anti-inflammatory compound of the Chinese herbal medicine Tripterygium wilfordii Hook. f. (Celastraceae).

Tie2-R849W mutant in venous malformations chronically activates a functional STAT1 to modulate gene expression.

Tie2 is an endothelial receptor tyrosine kinase. An amino-acid substitution of tryptophan for arginine at residue 849 (Tie2-R849W) leads to a ligand-independent activation of its kinase activity. This mutation has been associated with familial venous malformations (VMs), manifested by variable thickness or lack of smooth-muscle cells in the veins of patient lesions.

Anti-angiogenesis mediated by angiostatin K1-3, K1-4 and K1-4.5. Involvement of p53, FasL, AKT and mRNA deregulation.

The molecular mechanism mediated by multiple forms of angiostatin via acting on proliferating vascular endothelium remains elusive. To address whether three forms of angiostatin, K1-3, K1-4 or K1-4.5, utilized similar or distinct pathways to mediate anti-angiogenesis, we adopted an adenoviral expression system to express secretable angiostatin molecules for CM collection.

CC chemokines induce neutrophils to chemotaxis, degranulation, and alpha-defensin release.

We have previously shown that a Taiwanese cohort of HIV-uninfected individuals was associated with the significantly elevated levels of serum beta-chemokines, macrophage inflammatory protein (MIP-1)-alpha and MIP-beta, and RANTES. In the present study, we report that the members of this cohort have significantly greater numbers of lower buoyant-density neutrophils in their blood, which leads to further investigation of the effects of beta-chemokines on neutrophils. By electron and confocal microscopic techniques and FACScan, the results demonstrated that MIP-1alpha, MIP-beta, and/or RANTES readily activated the cells to release a large quantity of alpha-defensins in vitro through the degranulation process, which was the cause of low-buoyant-density neutrophil production.