Review Article

The Role of Costimulatory Receptors of the Tumour Necrosis Factor Receptor Family in Atherosclerosis

Table 2

TNF superfamily members and their role in atherosclerosis.

Receptor/ligand pairExperimental modelRole in atherosclerosisRef.

CD40/CD40LAnimal modelsMainly proatherogenic effects (demonstrated by administration of neutralising antibodies to CD40; deletion of CD40L)[5355]
Human atherosclerosisCD40 and CD40L are expressed in atherosclerotic plaques
Increased levels of serum sCD40L in unstable angina; correlate with poor prognosis
Polymorphisms in the CD40 gene associate with unstable plaques and increased risk of ACS
[49, 61, 62]

OX40/OX40LAnimal modelsMainly proatherogenic effects (demonstrated by targeted deletion of OX40; administration of neutralising antibodies to OX40L).
Human atherosclerosisPolymorphisms in the genes for OX40 or OX40L associate with myocardial infarction and CAD severity; OX40 and OX40L upregulated in atherosclerotic tissue or circulating immune cells; sOX40L serum levels increased in ACS patients and associated with higher risk of AMI[83, 88, 90]

4-1BB/4-1BBLAnimal modelsPromotes atherogenesis (demonstrated by administration of agonist antibody anti-4-1BB; deletion of 4-1BB).[104, 107, 108]
Human atherosclerosis4-1BB is expressed in atherosclerotic plaques; increased levels on circulating immune cells; serum levels of s4-1BB increased in ACS patients[109, 110]

CD27/CD70Human atherosclerosisCD27 and CD70 are present in atherosclerotic plaques.
CD27+Treg cell subtype levels decreased in patients with myocardial infarction
[122124]

CD30/CD30LHuman atherosclerosisJust one study available with inconclusive results[170]

HVEM/LIGHTHuman atherosclerosisHVEM and LIGHT detected in atherosclerotic plaques.
Elevated plasma levels of LIGHT in plasma of unstable angina and ischemic (atherosclerotic) stroke patients
[148151]

GITR/GITRLHuman atherosclerosisGITR and GITRL present in atherosclerotic plaques.
Decreased numbers of GITR+ Treg cells in atherosclerotic lesions
[152, 153]