Role of TNF-alpha in vascular dysfunction.
Role of TNF-alpha in vascular dysfunction.
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DOI：
10.1042/cs20080196
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发表时间：
2009-02
期刊：
影响因子：
--
通讯作者：
Zhang C
中科院分区：
文献类型：
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作者：
Zhang H;Park Y;Wu J;Chen Xp;Lee S;Yang J;Dellsperger KC;Zhang C
健康的血管功能主要受多种因素的调节，包括内皮依赖性松弛因子(EDRF)、内皮依赖性收缩因子(EDCF)和内皮依赖性超极化因子(EDHF)。由衰老、吸烟、炎症、创伤、高脂血症和高血糖引起的血管功能障碍或损伤是导致许多心血管疾病如高血压、糖尿病和动脉粥样硬化的众多危险因素之一。然而，血管活动受损的确切机制仍未解决，目前也没有科学共识。越来越多的证据表明，炎性细胞因子肿瘤坏死因子-α在体内和体外的大血管和微血管循环障碍中起着关键作用。AGEs(晚期糖基化终产物)/RAGE(AGEs受体)、LOX-1[凝集素样氧化型低密度脂蛋白受体-1]和核因子κB(核因子κB)信号通路通过增加循环和/或局部血管α-α的产生而在肿瘤坏死因子-DNA的表达中发挥关键作用。肿瘤坏死因子-α的表达增加导致ROS的产生，在许多病理生理条件下导致内皮功能障碍。脂代谢、膳食补充剂和体力活动影响肿瘤坏死因子-α的表达。肿瘤坏死因子-α和干细胞之间的相互作用在血管修复或再生方面也很重要。对这些因素的仔细研究可能有助于阐明导致血管功能障碍的机制。本综述的重点是总结最近显示肿瘤坏死因子-α在心血管疾病血管功能障碍中的作用的证据。我们相信，这些发现可能会在未来的治疗中提示针对炎症的新方向。
Healthy vascular function is primarily regulated by several factors including EDRF (endothelium-dependent relaxing factor), EDCF (endothelium-dependent contracting factor) and EDHF (endothelium-dependent hyperpolarizing factor). Vascular dysfunction or injury induced by aging, smoking, inflammation, trauma, hyperlipidaemia and hyperglycaemia are among a myriad of risk factors that may contribute to the pathogenesis of many cardiovascular diseases, such as hypertension, diabetes and atherosclerosis. However, the exact mechanisms underlying the impaired vascular activity remain unresolved and there is no current scientific consensus. Accumulating evidence suggests that the inflammatory cytokine TNF (tumour necrosis factor)-α plays a pivotal role in the disruption of macrovascular and microvascular circulation both in vivo and in vitro. AGEs (advanced glycation end-products)/RAGE (receptor for AGEs), LOX-1 [lectin-like oxidized low-density lipoprotein receptor-1) and NF-κB (nuclear factor κB) signalling play key roles in TNF-α expression through an increase in circulating and/or local vascular TNF-α production. The increase in TNF-α expression induces the production of ROS (reactive oxygen species), resulting in endothelial dysfunction in many pathophysiological conditions. Lipid metabolism, dietary supplements and physical activity affect TNF-α expression. The interaction between TNF-α and stem cells is also important in terms of vascular repair or regeneration. Careful scrutiny of these factors may help elucidate the mechanisms that induce vascular dysfunction. The focus of the present review is to summarize recent evidence showing the role of TNF-α in vascular dysfunction in cardiovascular disease. We believe these findings may prompt new directions for targeting inflammation in future therapies.