Atorvastatin Reduces the Expression of COX-2 mRNA in Peripheral Blood Monocytes from Patients with Acute Myocardial Infarction and Modulates the Early Inflammatory Response

Abstract

Background: We examined the effect of atorvastatin on the expression of COX-2 in peripheral blood monocytes from patients with early stage of acute myocardial infarction (AMI), and the plasma C-reactive protein (CRP) concentrations were also examined. Methods: Patients with AMI (n = 40) and with stable coronary heart disease (CHD; n = 18) were registered, and patients with AMI were randomly separated to a group that received routine therapy (group A, n = 20) or to a group that received routine therapy plus atorvastatin at 20 mg/day (group B, n = 20) for a week. Peripheral blood monocytes from patients with AMI both before and after treatment and from patients with stable CHD were isolated and cultured for 24 h. COX-2 mRNA expression was analyzed by reverse transcription-PCR. We measured concentrations of CRP in plasma by ELISA. Results: COX-2 expression was activated in peripheral blood monocytes from patients with AMI [0.92 (0.13)] compared with patients with stable CHD [0.19 (0.08)]; after a week of treatment, COX-2 expression in group B (reduced by 66%) was obviously lower than in group A (reduced by 24%; P <0.05). Plasma concentrations of CRP from patients with AMI [43.3 (14.9) mg/L] were increased compared with those from patients with stable CHD [1.65 (0.78) mg/L; P <0.05]; after a week of treatment, CRP concentrations in group B (reduced by 62%) were lower than in group A (reduced by 35%; P <0.05). COX-2 expression in peripheral blood monocytes from patients with AMI was positively correlated with plasma CRP concentration (r = 0.662; P <0.05). Conclusions: COX-2 may promote acute inflammatory process after AMI. Atorvastatin may improve the antiinflammatory effects through the COX-2 pathway.

Induction of hepatic cyclooxygenase-2 by hyperhomocysteinemia via nuclear factor-κB activation

“…9): 1) hyperhomocysteinemia induces COX-2 expression in rat liver; 2) COX-2 expression is mediated by NF-B activation; and 3) oxidative stress contributes to liver injury through activation of NF-B and subsequent induction of proinflammatory factor COX-2 during the initial phase of hyperhomocysteinemia. COX-2 is a proinflammatory factor that plays an important role in tissue damage during the early inflammatory response (9,24). Transgenic expression of COX-2 has been shown to exacerbate liver injury in murine models (17,51).…”

“…Induction of COX-2 has been detected in Kupffer cells (28), hepatocytes (17), and stellate cells (12). COX-2-mediated prostanoid generation is involved in early inflammatory response (9,24). It converts arachidonic acid into PGG 2 and subsequently PGH 2 that serves as a precursor for the synthesis of prostanoids, including PGs, thromboxanes (TXs), and prostacyclins (38).…”

Monocytes in Acute Coronary Syndromes

“…Increased monocyte expression of Mac-1 (CD11b/CD18) receptor, lymphocyte function associated antigen-1, and very late after activation antigen-4 promote monocyte attachment to the endothelium. 15 Monocyteassociated levels of intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), and L-selectin are also elevated from the early stages of ACS, either with or without myocardial necrosis being present. 15,16 Also, monocytes possess receptors to localize at sites of injured myocardium.…”

“…15 Monocyteassociated levels of intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), and L-selectin are also elevated from the early stages of ACS, either with or without myocardial necrosis being present. 15,16 Also, monocytes possess receptors to localize at sites of injured myocardium. The ACS-related upregulation of monocyte fibronectin receptor VLA-5 may be involved in their migration to tissue fibronectin, the latter being an important component of cardiac extracellular matrix.…”

Beneficial Actions of Polyunsaturated Fatty Acids in Cardiovascular Diseases: But, How and Why?

“…But, in none of these studies all the markers including hs-CRP, Lp-PLA 2, and MPO were measured simultaneously in the same study subjects to know which of them is the most reliable marker to predict cardiovascular events. In this context, it is interesting to note that treatment with statins decreased the plasma levels of hs-CRP, Lp-PLA 2 , MPO, monocyte chemoattractant protein-1 (MCP-1), IL-6, TNF-, free radicals, suppression of COX-2 and enhanced eNO suggesting that their beneficial actions, in part, could be attributed to the suppression of inflammation and enhancing the production of endothelial NO [98][99][100][101][102][103][104][105]. In addition, statins mediate some of their actions by modulating the metabolism of EFAs, which by them-selves or some of their products such as LXs, resolvins, and prostacyclin (PGI 2 ) are known to have anti-inflammatory actions [106, and see below] that, in part, could be responsible for the beneficial actions of statins.…”