Role of TNF-α in vascular dysfunction

Abstract

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.

Smoking Status is Associated with Serum High Molecular Adiponectin Levels in Community-Dwelling Japanese Men

“…Several studies also suggest that smoking induces production of inflammatory cytokines such as TNFand CRP 26) that are risk factors for atherosclerosis. Increased levels of TNF-and C-reactive protein (CRP) induce the production of ROS (reactive oxygen species), resulting in endothelial dysfunction under many pathophysiological conditions 27,28) . TNF-, whose produced is increased in an insulin-resistant state, also dose-dependently suppresses the expression of adiponectin in adipocytes by suppressing promoter activity 29) .…”

Fenofibrate protects endothelial cells against the harmful effects of TNF-alpha

“…In addition to our own previous findings, (40) others have also shown that TNF-α down-regulates eNOS and/or reduces NO production in various models of endothelial cells. (41)(42)(43) Furthermore, the induction of ROS generation by TNF-alpha, (44,45) as well as its pro-apoptotic effects (47,47) have extensively been described.…”

Visceral Obesity as a Risk Marker of Multiorgan Damage

“…Показано, что ЭЖ продуцирует про-воспалительные цитокины ИЛ-1, ИЛ-6 и ФНО-, а так-же хемокин МСР-1 (monocyticchemotactic protein-1), ока-зывая патологическое воздействие на сосудистое русло. Сужение сосудов, индуцированное ФНО-, свя-зано с увеличением производства ангиотензина II и эн-дотелина-1 [47]. Кроме того, TNF- уменьшает секре-цию адипонектина и стимулирует выработку других про-воспалительных веществ, тем самым способствуя поддержанию хронического воспалительного процес-са в жировой ткани.…”