Inhibition of vascular smooth muscle cell proliferation and neointimal formation in injured arteries by a novel, oral mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor.

Background: Mitogen-activated protein kinases (MAPKs) are rapidly induced after arterial injury in different animal models. However, their precise role in vascular smooth muscle cell (VSMC) proliferation and neointimal formation in vivo remains to be determined.

Methods And Results: We investigated the properties of a novel, selective inhibitor of the upstream kinase, MAPK/extracellular signal-regulated kinase, that is orally active (PD0185625).

Inhibition of hypoxia-induced angiogenesis by cigarette smoke exposure: impairment of the HIF-1alpha/VEGF pathway.

Smoking is a major risk factor for atherosclerotic diseases. However, the impact of cigarette smoke exposure on neovascularization that develops in response to tissue ischemia is unknown. Here we demonstrate that cigarette smoke extracts inhibit hypoxia-induced in vitro angiogenesis (matrigel assay) in human umbilical vascular endothelial cells.

Role of p44/p42 MAP kinase in the age-dependent increase in vascular smooth muscle cell proliferation and neointimal formation.

Objective: Age-dependent increase in vascular smooth muscle cell (VSMC) proliferation is thought to contribute to the pathology of atherosclerotic diseases. In this study, we investigated the role of mitogen-activated protein kinases (MAPKs) on VSMC proliferation and neointimal formation in the context of aging.

Methods And Results: VSMCs were isolated from the aorta of young and old rabbits.

Age-dependent impairment of reendothelialization after arterial injury: role of vascular endothelial growth factor.

Background: The mechanisms responsible for the association between advanced age and atherosclerotic diseases are not clear. Because atherosclerosis develops in response to local endothelial injuries, we investigated the effect of aging on vascular healing and reendothelialization.

Methods And Results: Endothelium denudation was performed by balloon angioplasty of the iliac arteries in young and old New Zealand White rabbits.