The CD40/CD40 ligand system: linking inflammation with atherothrombosis

J Am Coll Cardiol. 2009 Aug 18;54(8):669-77. doi: 10.1016/j.jacc.2009.03.076.


The role of CD40/CD40 ligand (CD40L) in atherothrombosis is now widely accepted. However, the exact mechanisms linking the CD40/CD40L system and the soluble form of CD40 ligand (sCD40L) with atherothrombosis are currently a topic of intensive research. CD40L and sCD40L belong to the tumor necrosis factor superfamily, and they are molecules with a dual prothrombotic and proinflammatory role. They are expressed in a variety of tissues such as the immune system (in both B and T cells), the vascular wall, and activated platelets. Soluble CD40L has multiple autocrine, paracrine, and endocrine actions, and it may trigger key mechanisms participating in atherothrombosis. CD40/CD40L may participate in the development of coronary atherosclerosis and the triggering of acute coronary syndromes, while sCD40L seems to have a prognostic role not only in subjects with advanced atherosclerosis but also in the general population. Although conventional cardiovascular medication such as antiplatelet therapy, statins, angiotensin-converting enzyme inhibitors, and many others have been shown to reduce both sCD40L and cardiovascular risk, it is still unclear whether specific treatments targeting the CD40/CD40L system will prove to be beneficial against atherothrombosis in the near future.

Publication types

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

MeSH terms

  • Acute Coronary Syndrome / genetics
  • Acute Coronary Syndrome / immunology
  • Acute Coronary Syndrome / physiopathology*
  • Animals
  • Atherosclerosis / immunology
  • Atherosclerosis / physiopathology*
  • CD40 Antigens / physiology*
  • CD40 Ligand / genetics
  • CD40 Ligand / physiology*
  • Coronary Artery Disease / immunology
  • Coronary Artery Disease / physiopathology
  • Humans
  • Platelet Activation / physiology
  • Polymorphism, Genetic
  • Prognosis
  • Solubility
  • Thrombosis / immunology
  • Thrombosis / physiopathology*


  • CD40 Antigens
  • CD40 Ligand