TY - JOUR
T1 - The complement component C5a is present in human coronary lesions in vivo and induces the expression of MMP-1 and MMP-9 in human macrophages in vitro
AU - Speidl, Walter S.
AU - Kastl, Stefan P.
AU - Hutter, Randolph
AU - Katsaros, Katharina M.
AU - Kaun, Christoph
AU - Bauriedel, Gerhard
AU - Maurer, Gerald
AU - Huber, Kurt
AU - Badimon, Juan J.
AU - Wojta, Johann
PY - 2011/1
Y1 - 2011/1
N2 - The complement component C5a is formed during activation of the complement cascade and exerts chemotactic and proinflammatory effects. Macrophages, which are localized in the rupture-prone shoulder regions of coronary plaques, are thought to play a major role in plaque destabilization and rupture through the production of matrix metalloproteinases (MMPs). When human monocyte-derived macrophages were stimulated in vitro with C5a, MMP-1 and MMP-9 mRNA levels were significantly increased. Furthermore, C5a up-regulated MMP-1 and MMP-9 antigens and activity, as determined by ELISA and specific activity assays. These effects were blocked by antibodies against the receptor C5aR/CD88. In addition, blocking experiments revealed that MMP-1 expression was mediated by activation of the transcription factor AP-1, and MMP-9 expression was induced by activation of NF-κB and AP-1. Immunohistochemical analysis of human coronary plaques demonstrated the colocalization of C5a, MMP-1, and MMP-9 in vivo. Together, these observations indicate that activation of the complement cascade and formation of C5a may play a role in the onset of acute coronary events by induction of MMPs in atherosclerotic lesions.-Speidl, W. S., Kastl, S. P., Hutter, R., Katsaros, K. M., Kaun, C., Bauriedel, G., Maurer, G., Huber, K., Badimon, J. J., Wojta, J. The complement component C5a is present in human coronary lesions in vivo and induces the expression of MMP-1 and MMP-9 in human macrophages in vitro.
AB - The complement component C5a is formed during activation of the complement cascade and exerts chemotactic and proinflammatory effects. Macrophages, which are localized in the rupture-prone shoulder regions of coronary plaques, are thought to play a major role in plaque destabilization and rupture through the production of matrix metalloproteinases (MMPs). When human monocyte-derived macrophages were stimulated in vitro with C5a, MMP-1 and MMP-9 mRNA levels were significantly increased. Furthermore, C5a up-regulated MMP-1 and MMP-9 antigens and activity, as determined by ELISA and specific activity assays. These effects were blocked by antibodies against the receptor C5aR/CD88. In addition, blocking experiments revealed that MMP-1 expression was mediated by activation of the transcription factor AP-1, and MMP-9 expression was induced by activation of NF-κB and AP-1. Immunohistochemical analysis of human coronary plaques demonstrated the colocalization of C5a, MMP-1, and MMP-9 in vivo. Together, these observations indicate that activation of the complement cascade and formation of C5a may play a role in the onset of acute coronary events by induction of MMPs in atherosclerotic lesions.-Speidl, W. S., Kastl, S. P., Hutter, R., Katsaros, K. M., Kaun, C., Bauriedel, G., Maurer, G., Huber, K., Badimon, J. J., Wojta, J. The complement component C5a is present in human coronary lesions in vivo and induces the expression of MMP-1 and MMP-9 in human macrophages in vitro.
KW - Atherosclerosis
KW - Matrix metalloproteinase
KW - Plaque rupture
UR - http://www.scopus.com/inward/record.url?scp=79251567642&partnerID=8YFLogxK
U2 - 10.1096/fj.10-156083
DO - 10.1096/fj.10-156083
M3 - Article
C2 - 20813982
AN - SCOPUS:79251567642
SN - 0892-6638
VL - 25
SP - 35
EP - 44
JO - FASEB Journal
JF - FASEB Journal
IS - 1
ER -