The CD163-expressing macrophages recognize and internalize TWEAK: potential consequences in atherosclerosis.
BACKGROUND
CD163 is a new potential scavenger receptor of Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) which elicits diverse biologic actions involved in atherosclerosis. We have analyzed the importance of TWEAK-CD163 interaction in atherosclerosis.


METHODS
TWEAK and CD163 interaction was studied in cultured human macrophages. Moreover, TWEAK and CD163 expression was analyzed in carotid atherosclerotic plaques (immunohistochemistry) and plasma (ELISA). We have also assessed their potential association with intima/media thickness (IMT) in asymptomatic subjects.


RESULTS
In vitro studies revealed that CD163-expressing macrophages can bind and internalize TWEAK protein exogenously added from supernatants. Accordingly, we observed an inverse correlation between the expression of CD163 and TWEAK (r=-0.51; p=0.008) in the shoulder region of atherosclerotic plaques obtained from 25 patients undergoing carotid endarterectomy. The same trend was observed when we analyzed the plasma concentration of both proteins in 90 subjects free from clinical cardiovascular disease (r=-0.25; p=0.016) in which carotid ultrasonography was performed to determine IMT. In these subjects, we found a positive correlation between sCD163 and IMT (r=0.36; p<0.001) and between sCD163-sTWEAK ratio and IMT (r=0.51; p<0.001). This association remained significant after adjusting for traditional cardiovascular risk factors and inflammatory markers explaining 39% (sCD163) or 48% (sCD163-sTWEAK ratio) of IMT variance.


CONCLUSIONS
Our results suggest that TWEAK-CD163 interaction takes place in vivo, probably decreasing TWEAK plasma concentration. Furthermore, we have observed that CD163-TWEAK plasma ratio is a potential biomarker of clinical and subclinical atherosclerosis.
Moreno
Juan A
JA
Vascular Research Lab, Fundación Jiménez Díaz, Autonoma University, Avda Reyes Catolicos 2, 28040 Madrid, Spain.
Muñoz-García
Begoña
B
Martín-Ventura
Jose L
JL
Madrigal-Matute
Julio
J
Orbe
Josune
J
Páramo
Jose A
JA
Ortega
Luis
L
Egido
Jesús
J
Blanco-Colio
Luis M
LM
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000276:immunology* / Q000378:metabolism / Q000601:surgery; D002460:Cell Line; D000074049:Cytokine TWEAK; D016894:Endarterectomy, Carotid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index; D013997:Time Factors; D048069:Tumor Necrosis Factors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D014463:Ultrasonography; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D000074049:Cytokine TWEAK; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C109743:TNFSF12 protein, human; D048069:Tumor Necrosis Factors