DAF Protects Against Atherosclerosis

Atherosclerosis describes any hardening and loss of elasticity of the arteries due to a build-up of fatty material such as cholesterol. Activation of the complement system, which consists of a cascade of small proteins that can result in cell lysis or trigger inflammation, plays a regulatory role in atherosclerotic lesion development. However, whereas proximal members of the complement pathway have a protective role, distal components are atherogenic.

DAF regulates complement activation at the C3 (proximal) level, but its role in atherosclerotic lesion development remains unclear. Leung et al hypothesized that DAF plays a protective role in atherosclerosis. Using a DAF-deficient mouse model of atherosclerosis, they found that DAF-deficient animals had increased levels of the distal complement components C5b-9 in aortic lesions. Lesions in DAF-deficient mice had accelerated development and increased size and complexity compared with normal animals. DAF, therefore, plays an essential regulatory role in limiting complement activation on the arterial wall and is protective against atherosclerosis.

This study by Leung et al "underlines the importance of DAF in shielding the arterial wall from the atherogenic effects of complement."