Role of TNF-alpha in vascular dysfunction

Clin Sci (Lond). 2009 Feb;116(3):219-30. doi: 10.1042/CS20080196.


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)-alpha 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-kappaB (nuclear factor kappaB) signalling play key roles in TNF-alpha expression through an increase in circulating and/or local vascular TNF-alpha production. The increase in TNF-alpha 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-alpha expression. The interaction between TNF-alpha 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-alpha in vascular dysfunction in cardiovascular disease. We believe these findings may prompt new directions for targeting inflammation in future therapies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Aging / metabolism
  • Animals
  • Dietary Carbohydrates / adverse effects
  • Dietary Fats / adverse effects
  • Endothelium, Vascular / physiopathology
  • Exercise / physiology
  • Humans
  • Lipid Metabolism / physiology
  • Reactive Oxygen Species / metabolism
  • Stem Cells / physiology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / physiology*
  • Vascular Diseases / physiopathology*


  • Dietary Carbohydrates
  • Dietary Fats
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha