[Atorvastatin reduces the expression of COX-2 mRNA in peripheral blood monocytes in patients with acute myocardial infarction and modulates the early inflammatory response].
OBJECTIVE
To measure the effect of atorvastatin on COX-2 expression in monocytes in patients with acute myocardial infarction (AMI).


METHODS
Forty patients with AMI (AMI group) and 18 patients with stable coronary heart disease (control group) were enrolled, and patients with AMI were randomly given routine therapy (n = 20) and routine therapy plus atorvastatin (20 mg/day, n = 20) for a week. Peripheral blood monocytes for each participant including patients with AMI were isolated and cultured for 24 hours. During the culture, monocytes in patients with pretreatment AMI were incubated with celecoxib in different concentration (0, 0.1, 1 and 10 micromol/L). COX-2 mRNA expression in monocytes was measured by reverse transcription polymerase chain reaction (RT-PCR); concentrations of interleukin-6 (IL-6) in supernatant from monocytes and plasma hs-CRP levels were measured by using enzyme-linked immunosorbent assay (ELISA).


RESULTS
COX-2 expression in monocytes in patients with AMI (0.92 +/- 0.13) was significantly higher than that in the control subjects (0.19 +/- 0.08), and decreased by 66% after atorvastatin (compared with that on routine therapy, P < 0.05); IL-6 secretions of monocytes in the AMI group (204.8 +/- 45.6 ng/L) increased dramatically compared with those in the control group (40.9 +/- 1.2 ng/L, P < 0.05), and reduced dramatically by 58% when incubated with 10 micromol/L celecoxib (P < 0.05) in a concentration-dependent manner; plasma levels of CRP in the AMI group (43.3 +/- 14.9 mg/L) significantly increased compared with those in the control group (1.7 +/- 0.8 mg/L), and reduced by 62% after atorvastatin (compared with those in the routine therapy group, P < 0.05). COX-2 expression in monocytes in the AMI group was positively correlated with both secretions of IL-6 and plasma level of CRP (r = 0.636 and 0.662, respectively, both P < 0.05).


CONCLUSIONS
There is an inflammatory activation in peripheral blood monocytes in patients with early AMI, and the monocytes-derived COX-2 may play an important role in promoting early inflammatory process. Atorvastatin may decrease COX-2 expression in peripheral blood monocytes in patients with AMI and cyclooxygenase-dependent pathway might be correlated with the anti-inflammation mechanism of statin.
Deng
Ping
P
Department of Cardiology, Changsha Central Hospital, Changsha 410011, China.
Zhao
Shui-ping
SP
Wu
Jie
J
Hong
Shao-cai
SC
Wu
Zhi-hong
ZH
Zhou
Hong-nian
HN
Nie
Sai
S
D000368:Aged; D000069059:Atorvastatin; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism*; D011758:Pyrroles / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics
D006538:Heptanoic Acids; D015850:Interleukin-6; D011758:Pyrroles; D012333:RNA, Messenger; D000069059:Atorvastatin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human