1 mg/ml) for 30 min. Evans blue dye leakage into the trachea induced by gaseous formaldehyde or

intravenous capsaicin was measured as an index of tachykinin NK1 receptor-mediated vascular permeability. Expression of substance P-immunoreactive nerves, tachykinin NK1 receptors, tumor necrosis factor (TNF)-alpha and NGF in the trachea was also Oligomycin A mw assessed immunohistochemically. Neurogenic plasma leakage in the trachea increased significantly between 7 and 21 days after LPS inhalation. Expression of TNF-alpha, NGF, substance P-immunoreactive nerves and tachykinin NK1 receptors was enhanced, peaking at 28 h, 7 days, 14 days and 14 days after LPS inhalation, respectively. Pretreatment with infliximab, a blocking antibody for TNF-alpha, almost completely abolished the airway changes seen after LPS inhalation. In conclusion, inhaled LPS increased innervation of sensory C-fibers and expression of tachykinin NK1 receptors in the airway, probably resulting in enhancement of neurogenic airway inflammation. These airway responses may be caused by overproduction of neurotrophins including NGF, mainly through a TNF-alpha-mediated pathway. ABT263 (C) 2011 Elsevier Inc. All rights reserved.”
“Objective: The mechanism of postangioplasty restenosis remains poorly understood. Low molecular weight (LMW) heparin has

been shown to inhibit the proliferation of vascular smooth muscle cells (VSMCs), which is the principal characteristic of restenosis. Studies have

shown that LMW heparin could bind to CD44. We hypothesized that LMW heparin might modulate CD44 expression thereby decreasing vascular remodeling.

Methods: Vascular remodeling was induced in CD44(+/+) and CD44(-/-) mice and treated with LMW heparin. The arteries were harvested for histologic assessment and determination of CD44 expression. Bone marrow transplantation was introduced Idelalisib cost to further explore the role and functional sites of CD44. Effects of LMW heparin on growth capacity, CD44 expression were further studied using the cultured mouse VSMCs.

Results: Transluminal injury induced remarkable remodeling in mouse femoral artery (sham wall thickness percentage [WT%]: 3.4 +/- 1.2% vs injury WT%: 31.8 +/- 4.7%; P < .001). LMW heparin reduced the remodeling significantly (WT%: 17.8 +/- 3.5%, P < .005). CD44(-/-) mice demonstrated considerably thicker arterial wall remodeling (WT%: 46.2 +/- 7.6%, P = .0035), and CD44-chimeric mice exhibited equal contributions of the local and circulating CD44 signal to the neointima formation. LMW heparin markedly upregulated CD44 expression in the injured femoral arteries. In vitro, LMW heparin decreased mouse VSMC growth capacity and upregulated its CD44 expression simultaneously in a dose-dependent and time-dependent manner, which could be partially blocked by CD44 inhibitor.

Conclusions: LMW heparin inhibits injury-induced femoral artery remodeling, at least partially, by upregulating CD44 expression.