This study demonstrated that the systemic levels of CRP, MPO, sCD40L and PlGF were significantly higher in ACS compared to CSA patients. The role of inflammation in the pathogenesis of myocardial infarction has been targeted in many studies. Numerous investigations have indicated CRP as a risk marker for the prediction of risk for future cardiovascular events [12, 13]. The association of CRP with cardiovascular disease is often related to inflammation. CRP is produced entirely by hepatocytes during the acute inflammatory response. However, several studies have also suggested that atherosclerotic tissue itself can release CRP .
Platelets are a source of inflammatory mediators . The activation of platelets following inflammation is a critical component of atherothrombosis process . The lymphocytes actively release sCD40L after platelet stimulation [17, 18], which eventually stimulate vascular endothelial cells inflammation by the secretion of chemokines and cytokines .
Myocardial cell damage is not only related to platelet activation and inflammation, but it is also preceded by the recruitment and activation of polymorphonuclear neutrophils. The polymorphonuclear neutrophils release MPO into circulation, resulting in higher MPO level in ACS patients [19, 20]. Myeloperoxidase promotes plaque fibrous cap weakening by activating MMPs  and deactivating MMPs inhibitors .
C-reactive protein, MPO, PlGF and sCD40L are not solely produced from human coronary plaque. They can be released systemically from other sources such as liver (CRP), circulating neutrophils (MPO), endothelial cells (PlGF) or circulating platelets (sCD40L). Therefore, the elevated markers in ACS patients could be caused by the substantial release from ruptured coronary plaques or produced by the occluded coronary arteries. Besides, there is a possibility that the markers are released systemically from stimulated non-coronary source, reach the coronary plaque site through blood circulation and trigger plaque rupture. In order to investigate the possible site of origin of the markers responsible in the pathogenesis of ACS, both local intracoronary and systemic concentrations of markers were measured, which was the primary aim of this study.
This study showed no significant difference between levels of CRP, MPO and sCD40L in the coronary circulation compared to systemic venous blood, in the ACS patients. Therefore, we speculate that the markers are mainly released from the non-coronary site. The non-coronary source is possibly triggered by a specific precursor prior to the release of the marker, which eventually contribute to the plaque rupture in ACS patients. However, since the time to sample collection after onset of symptom in ACS patients was quite long and up to 48 h, these biomarkers could be carried from coronary local lesion to the systemic circulation, especially if the markers were produced at an early stage of symptom. Hence, future study targeting blood sampling at multiple time intervals after onset of symptom in ACS patients should carried out to answer this hypothesis.
In contrast, the level of PlGF in the coronary circulation was significantly higher than its level in the systemic circulation of ACS patients. Hence, this finding predicted its elevation in ACS patients could be caused by the substantial release from ruptured coronary plaques or produced by the occluded coronary arteries, rather than by non-cardiac origin source. This finding and speculation were further supported by a study conducted by Iwama et al. . This study indicated that vascular tissue, especially the endothelium within the infarct myocardium can substantially produce PlGF during acute myocardial infarction.
C-reactive protein has been detected in human coronary plaques [22, 23]. The generation of CRP and its complement has been reported in atherosclerotic plaque tissue , particularly the unstable plaque showed increased expression of CRP protein . Indeed, human coronary artery smooth muscle cells can produce CRP in response to cytokines . Since there was no increased CRP level in the coronary circulation, we hypothesized the increased production of CRP from systemic hepatic cells resulted in the markedly elevation of CRP in ACS patients. The result showed there was a significant decrease in coronary CRP in CSA patients. We may attribute the decrease to local uptake and catabolism of the protein by phagocytes in coronary plaque site. This speculation is supported by immunohistochemistry studies that showed the thrombi at culprit site contained phagocytic white blood cells with the presence of CRP .
Numerous studies have demonstrated higher concentration of protein markers in the systemic blood of ACS patients compared to CSA. However, the comparisons between marker concentrations in coronary circulation at the site of lesion with systemic circulation were merely studied. The present study used a particular method to sample blood from coronary arteries. Coronary blood was collected from the coronary circulation at the site of the culprit lesion, where the level of those markers is expected to be the highest if they are released from the ruptured atherosclerotic plaque.
Coronary CRP levels demonstrated a non significant positive correlation with coronary MPO, sCD40L and PlGF levels. The weak correlations suggested the markers reflect distinct signal pathways other than systemic inflammation that eventually contribute to a pro-inflammatory and pro-coagulating environment in the coronary circulation.
Upon released by activated PMNs, MPO transform the plaque into unstable form with large lipid core and thin fibrous cap. Soluble CD40 ligand released after platelet activation trigger an inflammatory response in vascular endothelial cells by the secretion of cytokines and chemokines. In addition to inflammatory properties, sCD40L stabilizes platelet–platelet aggregates and initiates further platelet activation during thrombosis after plaque rupture. PlGF stimulates vascular inflammation by promoting endothelial activation and macrophage recruitment into atherosclerotic lesions.
However, there is limitation in this study. We only managed to obtain coronary blood sample from coronary ostium in CSA patients since the use of export aspiration catheter is not a routine practice in percutaneous transluminal coronary angioplasty (PTCA) procedure for CSA patients.