Thrombolytic Therapy Up-regulates Inflammatory Mediators Compared to Percutaneous Coronary Intervention (PCI).

The important role of reperfusion therapies in the treatment of acute myocardial infarction is well documented. However, reperfusion therapies can initiate inflammatory response and may damage the myocardium. The purpose of current study was to compare the effects of percutaneous coronary intervention and thrombolytic therapy on inflammatory markers in the setting of ST elevation myocardial infarction (STEMI). Eighty three patients with STEMI were enrolled in this study. 40 patients underwent percutaneous coronary intervention (PCI), and 43 patients received streptokinase (1.5 million IU) as a main medical reperfusion therapy. Monocyte expression of Toll-like receptor 4 (TLR4),  serum levels of TNF-α and IL-1ß, red cell distribution width (RDW) and C- reactive protein (CRP) were compared between groups at admission time, two hours and four hours after termination of treatment. p<0.05 was considered as statistically significant for all tests. Compared to baseline, both treatments increased monocyte expression of TLR4, serum levels of cytokines and CRP. Compared to PCI, medical reperfusion therapy significantly raised both monocyte expression of TLR4 (39.8±4.7 % vs 49.1±3.6 %, p<0.01), and serum levels of TNF-α (13.2±3.7 pg/ml vs 25.1±2.6pg/mlp<0.05). No effect was seen on RDW levels. Moreover, medical reperfusion therapy caused significant rise in CRP levels (p<0.01). The present study demonstrates that thrombolytic therapy is associated with higher inflammatory responses compared to PCI. Our findings suggest that thrombolytic therapy may increase the likelihood of detrimental effects of reperfusion therapy on the myocardium.

Everolimus-Eluting Stents Reduce Monocyte Expression of Toll-Like Receptor 4.

PURPOSE: Toll-like receptors (TLR) are well known components of the innate immune system. Among them, TLR4 is related to the inflammatory processes involved in atherosclerotic plaque formation. Our purpose was to compare the monocytic expression of TLR4 following implantation of drug-eluting (DES) and bare stents (BMS). METHODS: In this study, patients with chronic stable angina undergoing elective percutaneous coronary intervention (PCI) in ShahidMadani Heart Hospital, Tabriz, Iran were included. Ninety-five patients receiving DES and 95 patients receiving BMS were selected between 2012 and 2014.Everolimus eluting stents were implanted for DES group. Both groups received similar medications and procedure. Blood samples were taken before PCI, 2 hours and 4 hours after termination of PCI. Expression of TLR4 on monocytes was measured using flowcytometry. Patients were matched for age, sex and coronary artery disease risk factors, but not for TLR4 expression rate before PCI. RESULTS: A significant difference was seen between DES and BMS in TLR4 expression before (21.3±2.8% vs. 15.5±2.7%; P< 0.05) and four hours after PCI (30.1 ± 3.3% vs 39.2 ± 3.2%, P< 0.05). Due to the unmatched rate of TLR4+ expression before PCI, we measured the percentage of increase in TLR4 expression between groups. DES compared to BMS significantlycaused less increase in the TLR4 expression (50.23%±10.03% vs. 446.35%±70.58%, p<0.001). CONCLUSION: Our findings suggest thateverolimuseluted from the stents can decrease PCI induced increase in the TLR4 expression on the surface of monocytes.

Hydrocortisone reduces Toll-like receptor 4 expression on peripheral CD14+ monocytes in patients undergoing percutaneous coronary intervention.

BACKGROUND: Evidence from several lines of investigations suggests that Toll-like receptor 4 (TLR4) is involved in atherosclerosis as a bridge between innate and acquired immunity. Percutaneous coronary intervention (PCI) can trigger inflammation through activation of human TLR4 (hTLR4) on monocytes. Hydrocortisone as an anti-inflammatory and immuno-suppressant agent has multiple mechanisms of action. In this study, we aimed at assessing the effects of hydrocortisone on monocyte expression and activity of hTLR4 in patients underwent PCI. METHODS: Blood samples were taken from a total of 71 patients with chronic stable angina who were scheduled for a PCI, before the intervention. Thirty patients received 100 mg hydrocortisone prior to the procedure. Control group was composed of 41 patients underwent PCI without receiving hydrocortisone. Blood collection was repeated 2 and 4 h after PCI. The expression of hTLR4 on the surface of CD14+ monocytes and the serum levels of TNF-α and IL-1ß were measured using flowcytometry and Sandwich ELISA. RESULTS: Compared with controls, hydrocortisone significantly reduced monocyte expression of hTLR4 in test group (P<0.01). In addition, it had a significant effect on reduction of serum concentrations of TNF-α and IL-1ß in test group in a time-dependent manner (P<0.01). CONCLUSION: In this study, hydrocortisone was able to reduce the hTLR4/CD14 positive monocytes and its related pro-inflammatory cytokines, thus it can decrease inflammatory responses following PCI.

Monocyte expression of Toll-like receptor-4 in patients with stable angina undergoing percutanoeus coronary intervention.

BACKGROUND: Toll like receptors (TLRs) are well recognized players in inflammatory conditions. Among them TLR-4 is involved in chronic inflammatory processes such as formation of atherosclerotic plaques. OBJECTIVE: The present study was aimed to examine the effects of percutanoeus coronary intervention (PCI) as a revascularization method on monocyte expression of hTLR-4 and on the serum levels of two proinflammatory cytokines (TNF-α and IL-1ß). METHODS: Blood samples were obtained from 41 patients with stable angina who were candidates for PCI. The samples were collected immediately before and 2h and 4h after PCI. The expression of hTLR-4 on CD14+ monocytes and the serum levels of TNF-α and IL-1ß were measured using flowcytometry and ELISA techniques, respectively. RESULTS: By comparing the frequency of circulating hTLR-4+/CD14+ monocytes at different time points, it was observed that PCI procedure up regulates the monocyte expression of hTLR-4 (p<0.05). The increase in expression was associated with the elevation of the serum levels of proinflammatory cytokines (p<005). There was a significant correlation between monocyte expression of hTLR-4 and serum levels of TNF-α and IL-1ß only before PCI. In spite of parallel increase in the serum levels of proinflammatory cytokines and the monocyte expression of hTLR-4, the correlation did not attain a significant level after PCI intervals. CONCLUSION: PCI is positively associated with an increase in the monocyte expression of hTLR-4. It is also associated with the elevation in the serum levels of proinflmmatory cytokines. These findings suggest that hTLR-4 monocyte expression may be used as a potential prognostic tool in patients with stable angina undergoing PCI.