Hydrogen-rich saline prevents neointima formation after carotid balloon injury by suppressing ROS and the TNF-α/NF-κB pathway.

Reactive oxygen species (ROS) play a pivotal role in neointima hyperplasia after balloon injury. Molecular hydrogen has emerged as a novel antioxidant and has been proven effective in treating many diseases. We aimed to determine the mechanism by which hydrogen affects neointima formation. We assessed the influence of a hydrogen-rich saline solution (HRSS) by daily injection in rats. Rats were euthanized to evaluate the neointima. ROS, malondialdehyde (MDA) and superoxide dismutase (SOD) and reduced glutathione (GSH), were detected in the injured artery. Macrophage infiltration and the production of inflammatory factors (i.e., IL-6, TNF-α and NF-κB) were also observed. The in vitro effects of hydrogen on vascular smooth muscle cell (VSMC) proliferation were also measured. HRSS decreased the neointima area significantly. The neointima/media ratio was also reduced by HRSS. There was a decline in the number of PCNA-positive cells in the intima treated with HRSS. Meanwhile, HRSS ameliorated the ROS and MDA levels and increased SOD, reduced GSH levels in the injured carotid. In addition, the levels of inflammatory factors, such as IL-6, TNF-α and NF-κB p65, were attenuated by HRSS. In vitro studies also confirmed the anti-proliferative capability of the hydrogen solution and ROS generation in VSMCs induced by PDGF-BB. HRSS may have a protective role in the prevention of neointima hyperplasia and restenosis after angioplasty. HRSS may partially exert its role by neutralizing the local ROS and suppressing the TNF-α/NF-κB pathway.

Qin ZX ，Yu P ，Qian DH ，Song MB ，Tan H ，Yu Y ，Li W ，Wang H ，Liu J ，Wang Q ，Sun XJ ，Jiang H ，Zhu JK ，Lu W ，Huang L ... -  《-》

Naringenin inhibits angiotensin II-induced vascular smooth muscle cells proliferation and migration and decreases neointimal hyperplasia in balloon injured rat carotid arteries through suppressing oxidative stress.

Xu C ，Chen J ，Zhang J ，Hu X ，Zhou X ，Lu Z ，Jiang H ... -  《-》

A novel antioxidant 3,7-dihydroxy-isoflav-3-ene (DHIF) inhibits neointimal hyperplasia after vessel injury attenuating reactive oxygen species and nuclear factor-kappaB signaling.

Kanellakis P ，Pomilio G ，Walker C ，Husband A ，Huang JL ，Nestel P ，Agrotis A ，Bobik A ... -  《-》

Inhibition of neointimal hyperplasia in the rat carotid artery injury model by a HMGB1 inhibitor.

High mobility group box 1 protein (HMGB1) is expressed in atherosclerotic lesions. However, its role in vascular system is unknown. In this study, we explore whether the inhibition of HMGB1 attenuates neointimal formation in animal models. Experiments were performed with VSMCs from thoracic aorta of SD rats in vitro, and a rat carotid artery balloon injury model in vivo. HMGB1 levels were increased after stimulation of angiotensin II (Ang II) and 10% serum in cultured VSMCs. HMGB1 inhibitor (glycyrrhizin) significantly inhibited the proliferation and migration of Ang II-treated VSMCs, which was accompanied with decreased oxidative stress and inflammation. The underlying mechanisms were related with the promotion of antioxidant systems activity and deactivation of p38 MAPK/NF-κB signaling pathway, respectively. Furthermore, inhibition of HMGB1 blunted Notch signaling pathway during VSMCs phenotypic transition, and correspondingly restored VSMCs differentiated phenotype under 10% serum stimulation. In vivo study, HMGB1 expression was elevated after artery injury. Meanwhile, glycyrrhizin treatment suppressed HMGB1 expression, which was accompanied with blunted inflammation and oxidative stress after 7 days of balloon injury. Moreover, the area of neointimal to media area ratio was significantly decreased in glycyrrhizin group compared with injury group at 14 days after balloon injury. Inhibition of HMGB1 activity attenuated VSMCs activation and neointimal formation after carotid injury. Therefore, blockage of HMGB1 might represent a novel therapeutic strategy for vascular injury.

Chen J ，Zhang J ，Xu L ，Xu C ，Chen S ，Yang J ，Jiang H ... -  《-》

Nobiletin Inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and migration and attenuates neointimal hyperplasia in a rat carotid artery injury model.

Preclinical Research The abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) plays a pivotal role in the development of neointimal hyperplasia after vascular injury. Nobiletin, a citrus bioflavonoid, exhibits anti-inflammatory and anti-oxidative activities. The present study evalutaed whether nobiletin could inhibit platelet-derived growth factor (PDGF)-BB- stimulated VSMC proliferation and migration and decrease neointimal hyperplasia in a rat carotid artery injury model. Cultured VSMCs from rat thoracic aortas were treated with nobiletin before being stimulated with 20 ng/ml PDGF-BB, and rats were subjected to carotid artery injury. Nobiletin inhibited PDGF-BB-induced VSMC proliferation and migration, attenuated reactive oxygen species (ROS) production and reduced phosphorylation of ERK1/2 and the expression of nuclear NF-κB p65 in PDGF-BB-stimulated VSMCs. Nobiletin decreased the intima area and the ratio of neointima to media in balloon-injured rat carotid arteries. Serum levels of TNF-α and IL-6 in nobiletin-treated rats were decreased. These results indicated that nobiletin could be a potential protective agent for the prevention and treatment of restenosis after angioplasty.

Guan S ，Tang Q ，Liu W ，Zhu R ，Li B ... -  《-》