CD163 is a macrophage receptor of haptoglogin/ haemoglobin complexes responsible for clearance of hemogloin. It has been recently suggested to be a potential scavenger receptor for TWEAK (Tumor necrosis factor-like weak inducer of apoptosis). TWEAK levels were reported to be decreased in carotid atherosclerosis. Our hypothesis is that decreased circulating TWEAK could be paralleled by an increased presence of CD163-expressing macrophage in atherosclerotic plaques. Since peripheral artery disease (PAD) is an important manifestation of systemic atherosclerosis, we have assessed the levels of circulating TWEAK-CD163 in PAD.

Patients with PAD (n=184) had lower TWEAK (169.2±8.3vs 211.9±15.4pg/mL; p<0.05) and higher sCD163 (408.1±14.5vs 317.4±8.4ng/mL; p<0.05) plasma concentration than age-matched controls (n=330). After stratification according to the severity of disease, we observed that TWEAK/sCD163 ratio was significantly decreased in those patients with higher degree of disease (0.39±0.06vs 0.66±0.08, p<0.05) relative to the other groups. Analysis of conditioned medium obtained from cultured human atherosclerotic femoral plaque samples (n=38) and healthy aortas (n=14) revealed that higher amount of sCD163 was released by the atherosclerotic tissue, whereas TWEAK presented the opposite trend.

Our results suggest that CD163/TWEAK plasma ratio could be a potential biomarker of clinical peripheral artery disease. We can hypothesized that decreased levels of circulating TWEAK observed in atherosclerosis may be the result of a trapping by plaque macrophages through their CD163.