Effect of inflammatory factor‐induced cyclo‐oxygenase expression on the development of reperfusion‐related no‐reflow phenomenon in acute myocardial infarction

Abstract

SUMMARYNo reflow after reperfusion therapy for myocardial infarction is a strong predictor of clinical outcome. Increased levels of inflammatory factors, including C-reactive protein (CRP), in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) may affect myocardial perfusion. However, why the no-reflow phenomenon increases in inflammation stress after PCI is not clear. The aim of the present study was to determine the effects and molecular mechanisms underlying the effects of CRP on the expression of cyclo-oxygenase (COX) on the development of the no-reflow phenomenon. There was a significant increase in plasma levels of CRP and interleukin (IL)-6 in no-reflow patients, suggesting that inflammatory factors play an important role in the development of the no-reflow phenomenon. The mechanisms involved were further evaluated after reperfusion in a rat model mimicking the no-reflow phenomenon. Compared with normal reflow rats, there were significant increases in both COX-1 and COX-2 in cardiac tissue from noreflow rats. The COX inhibitor indomethacin (5 mg/kg, i.p.) significantly reduced the no-reflow area. In another series of experiments, human coronary artery endothelial cells (HCAEC) were treated with CRP at clinically relevant concentrations (5-25 lg/mL). C-Reactive protein significantly increased COX-1 and COX-2 levels in a time-and concentration-dependent manner. In addition, extracellular signal-regulated kinase (ERK) and Jun N-terminal kinase (JNK) were activated in CRP (5, 10, 25 lg/mL)-treated HCAEC cultures. Furthermore, the ERK inhibitor pd98059 (30 lmol/L) and the JNK inhibitor sp600125 (10 lmol/L) blocked CRP-induced COX-1 and COX-2 expression for 12 h.Together, the findings of the present study suggest that CRP can promote the development of the no-reflow phenomenon by increasing COX-1 and COX-2 expression, which is regulated, in part, via ERK and JNK activity.

Inflammatory and Hematological Indices as Simple, Practical Severity Predictors of Microdysfunction Following Coronary Intervention: A Systematic Review and Meta-Analysis

“…41 Experimental research revealed that CRP can promote the development of the no-reflow phenomenon by increasing cyclooxygenase-1 and cyclooxygenase-2 expression, which is regulated, in part, via extracellular signal-regulated kinase and Jun N-terminal kinase activity. 42…”

Elevated uric acid is related to the no‐/slow‐reflow phenomenon in STEMI undergoing primary PCI

“…Jiao reported that elevated CRP increases the expression of cyclooxygenase, in a time‐ and concentration‐dependent manner, resulting in NRP 29 . However, Niccoli found no significant correlation between CRP serum levels on admission and coronary artery NRP 30 …”

“…29 However, Niccoli found no significant correlation between CRP serum levels on admission and coronary artery NRP. 30 The underlying reason for the negative result may be that the sample size of the study was relatively small. Our study suggested that the CRP level, WBC, neutrophil to HDL-C ratio and monocyte to HDL-C ratio at admission in the hyperuricaemia group were higher than those in the non-hyperuricaemia group.…”

Cyclic Nucleotide-Directed Protein Kinases in Cardiovascular Inflammation and Growth

“…Factors secreted by neutrophils which include ROS, cytokines, and chemokines which promote inflammation may also damage previously viable tissue [ 68 ]. Neutrophils obstruct post-capillary venules contributing to microvascular dysfunction [ 85 ] which is thought to mediate no-reflow phenomenon associated with reperfusion injury [ 68 , 85 , 87 ]. Platelets recruited to sites of injury may also contribute to reperfusion injury and microvascular dysfunction by secreting vasoactive thromboxane A 2 and 5-HT.…”