Arteriosclerosis, thrombosis, and vascular biology
-
Arterioscler. Thromb. Vasc. Biol. · Apr 2013
Novel role of copper transport protein antioxidant-1 in neointimal formation after vascular injury.
Vascular smooth muscle cell (VSMC) migration is critically important for neointimal formation after vascular injury and atherosclerosis lesion formation. Copper (Cu) chelator inhibits neointimal formation, and we previously demonstrated that Cu transport protein antioxidant-1 (Atox1) is involved in Cu-induced cell growth. However, role of Atox1 in VSMC migration and neointimal formation after vascular injury is unknown. ⋯ Atox1 is involved in neointimal formation after vascular injury through promoting VSMC migration and inflammatory cell recruitment in injured vessels. Thus, Atox1 is a potential therapeutic target for VSMC migration and inflammation-related vascular diseases.
-
Arterioscler. Thromb. Vasc. Biol. · Apr 2013
Thioredoxin 1 is essential for sodium sulfide-mediated cardioprotection in the setting of heart failure.
The aim of this study was to determine whether thioredoxin 1 (Trx1) mediates the cardioprotective effects of hydrogen sulfide (H2S) in a model of ischemic-induced heart failure (HF). ⋯ These findings provide novel information that the upregulation of Trx1 by Na2S therapy in the setting of HF sets into motion events, such as the inhibition of apoptosis signaling kinase-1 signaling and histone deacetylase 4 nuclear export, which ultimately leads to the attenuationof left-ventricular remodeling.
-
Arterioscler. Thromb. Vasc. Biol. · Apr 2013
Redox-sensitive transcription factor Nrf2 regulates vascular smooth muscle cell migration and neointimal hyperplasia.
Reactive oxygen species are important mediators for platelet-derived growth factor (PDGF) signaling in vascular smooth muscle cells, whereas excess reactive oxygen species-induced oxidative stress contributes to the development and progression of vascular diseases, such as atherosclerosis. Activation of the redox-sensitive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), is pivotal in cellular defense against oxidative stress by transcriptional upregulation of antioxidant proteins. This study aimed to elucidate the role of Nrf2 in PDGF-mediated vascular smooth muscle cell migration and neointimal hyperplasia. ⋯ These findings suggest that the Nrf2 system is important for PDGF-stimulated vascular smooth muscle cell migration by regulating reactive oxygen species elimination, which may contribute to neointimal hyperplasia after vascular injury. Our findings provide insight into the Nrf2 system as a novel therapeutic target for vascular remodeling and atherosclerosis.
-
Arterioscler. Thromb. Vasc. Biol. · Apr 2013
Deletion of FHL2 gene impaired ischemia-induced blood flow recovery by modulating circulating proangiogenic cells.
The four and a half Lin11, Isl-1 and Mec-3 (LIM) domain protein 2 (FHL2) is a member of the four and a half LIM domain-only (FHL) gene family, and has been shown to play an important role in inhibiting inflammatory angiogenesis. Here, we tested the hypothesis that impaired ischemia-induced neovascularization in mice lacking FHL2 is related to a defect in proangiogenic cell mobilization and functions in vasculogenesis. ⋯ Deficiency of FHL2 impairs ischemia-induced neovascularization, and these suppressive effects may occur through a reduction in proangiogenic cell mobilization, migration, and vasculogenesis functions.