CXC-chemokines in coronary artery disease: possible pathogenic role of interactions between oxidized low-density lipoprotein, platelets and peripheral blood mononuclear cells.
CXC-chemokines may be involved in atherogenesis. Herein we examined the possible role of CXC-chemokines in the inflammatory interactions between oxidized (ox-) low-density lipoprotein (LDL), platelets and peripheral blood mononuclear cells (PBMC) in 15 patients with coronary artery disease (CAD) without 'traditional' risk factors and 15 carefully matched controls. Our main findings were: (a) ox-LDL stimulated the release of the CXC-chemokines interleukin (IL)-8, ENA-78 and GRO-alpha from PBMC, particularly in CAD. (b) In platelets, ox-LDL induced release of ENA-78 and, when combined with SFLLRN, also of GRO-alpha, with significantly higher response in CAD. (c) Platelet-rich plasma, especially when costimulated with ox-LDL, enhanced the release of IL-8 from PBMC, particularly in CAD patients. (d) Freshly isolated PBMC showed markedly increased IL-8 mRNA expression in CAD patients. Our findings suggest enhanced inflammatory interactions between ox-LDL, platelets and PBMC in CAD patients involving CXC-chemokine related mechanisms, possible contributing to atherogenesis in these and other CAD patients.
Holm
T
T
Department of Cardiology, Rikshospitalet, Oslo, Norway.
Damås
J K
JK
Holven
K
K
Nordøy
I
I
Brosstad
F R
FR
Ueland
T
T
Währe
T
T
Kjekshus
J
J
Frøland
S S
SS
Eiken
H G
HG
Solum
N O
NO
Gullestad
L
L
Nenseter
M
M
Aukrust
P
P
D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology / Q000235:genetics; D001792:Blood Platelets / Q000502:physiology*; D016022:Case-Control Studies; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D018925:Chemokines / Q000097:blood; D019743:Chemokines, CXC / Q000097:blood* / Q000235:genetics; D002630:Chemotactic Factors / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D016209:Interleukin-8 / Q000031:analogs & derivatives* / Q000097:blood / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D012307:Risk Factors
C475829:CXCL1 protein, human; C486263:CXCL5 protein, human; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein