NK cell apoptosis in coronary artery disease: relation to oxidative stress.
OBJECTIVE
Natural killer (NK) cells, key elements in initiation and modulation of immune responses, were recently found to be reduced in coronary artery disease (CAD). To clarify mechanisms behind this reduction, we here investigated NK cell apoptosis in CAD patients. Since oxidative stress has been linked to NK cell apoptosis, we related the findings to oxidative stress in vivo and evaluated the ex vivo susceptibility of NK cells to oxidized lipids.


RESULTS
The number of apoptotic NK cells in peripheral blood was significantly increased in CAD patients compared to controls. Purified NK cells from CAD patients also showed a higher rate of spontaneous apoptosis ex vivo. Dose- and time-dependent effects of oxidized LDL and 7beta-hydroxycholesterol (7betaOH) on apoptosis and ROS production were determined in NK cells from blood donors. Thereafter, purified NK cells from CAD patients and healthy controls were exposed to the oxidized lipids in a paired design. NK cells from patients were more susceptible to apoptosis induced by oxidized LDL, in particular 7betaOH, compared to cells from controls. Plasma measurements of LDL protein oxidation and lipid peroxidation did not show any differences between patients and controls. On the other hand, plasma carotenoids were significantly decreased in patients and inversely correlated to NK cell apoptosis rate.


CONCLUSIONS
The rate of spontaneous NK cell apoptosis was increased in CAD patients. Although NK cells in CAD patients were more sensitive to oxidized lipids ex vivo, indicating a mechanism contributing to the reduced NK cell activity in CAD, the data could not verify an obvious link between NK cell apoptosis and increased oxidative stress in vivo.
Li
Wei
W
Division of Pharmacology, Department of Medicine and Health Science, Faculty of Health Sciences, Linköping University, S-581 85 Linköping, Sweden. weili@imv.liu.se
Lidebjer
Caroline
C
Yuan
Xi-Ming
XM
Szymanowski
Aleksander
A
Backteman
Karin
K
Ernerudh
Jan
J
Leanderson
Per
P
Nilsson
Lennart
L
Swahn
Eva
E
Jonasson
Lena
L
D000368:Aged; D017209:Apoptosis / Q000276:immunology*; D002338:Carotenoids / Q000097:blood; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism* / Q000473:pathology*; D015227:Lipid Peroxidation / Q000276:immunology; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D018384:Oxidative Stress / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D002338:Carotenoids