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Thrombus formation in acute coronary syndromes: what is new?

ESC Congress 2010

Basic Sciences, Pharmacology, Genomics and Cardiovascular Pathology

This session was devoted to the presentation of late advances in the understanding of mechanism contributing to thrombosis in acute coronary syndromes. Four topics were selected to be discussed within this active area of investigation, new advances in the characterization of atherosclerotic plaque rupture and its thrombotic complications, the contribution of microparticles and micro RNAs to platelet activation and thrombus growth, new mechanisms of activation of tissue factor and the interaction between white cells with platelets.

Dr R. Virmani (Gaithersburg, USA) described the differential features between plaque rupture and plaque erosion, the two types of plaque that trigger acute coronary syndromes. While plaque rupture is better characterized, plaque erosion is less well known. “Erosions are lesions rich in smooth muscle cells with paucity of macrophages near the lumen and only 50% have a necrotic core. These are usually seen in younger patients (less than 50) and in females that often present with atypical chest pain” described Dr Virmani. Plaque progression is a complex process.

The earliest changes of atherosclerosis are the pathological intimal thickenings (PITs) with a lipid pool located close to the media. This lipid pool is devoid of smooth muscle cells and the luminal area may or may not contain macrophages. PITs are followed by macrophage infiltration into the lipid pool which eventually forms the necrotic core and eventually ruptures. In the early stages of atherosclerosis apoptotic bodies are efficiently removed by efferocytosis (engulfment), however the necrotic core is formed because of defective efferocytosis.

Dr. L.M. Biassuci (Rome, Italy) described a new area of investigation on the pathophysiology of coronary disease. Microparticles (MPs) are small vesicles (0.01-1um), membrane blebs, that are released from activated and apoptotic cells. MPs can be measured in the circulation thereby they may be biomarkers of cellular activation or dysfunction. Dr Biassuci presented data on the association of raised levels of circulating platelet microparticles with the thrombotic burden in ACS patients. He concluded that a lot of research is needed to precisely define the mechanisms of contribution of microparticles of diverse cellular origin (endothelial cells, smooth muscle cells, monocyte/macrophages and platelets) to cardiovascular disease.

Dr Biassuci briefly touched on the role of MicroRNAs, small-non coding single strand RNAs (about 22 nucleotides), that post-transcriptionally regulate the expression of a target gene. About 10-30% of the genome expression seems to be modulated by miRNAs. A high number of miRNAs has been reported to exist in the platelet, an organelle without a nucleus. Dr Biassuci concluded by emphasising that much research is needed in this area to fully understand their function.

Dr B Engelman (Munich, Germany) gave an excellent overview of the different pools of tissue factor in the vascular system and their contribution to thrombosis. “Protein disulphide isomerase (PDI) activation of Tissue Factor (TF) is the first step of blood coagulation” Dr Engelman concluded. He additionally described new findings in his lab regarding neutrophil serine proteases and extracellular nucleosomes as mediators of arterial thrombosis and physiological hemostasis. Interesting preliminary data was shown on the antithrombotic efficacy of a protease-resistant TFPI (tissue factor pathway inhibitor) mutant originally developed by Dr Engelman’s group.

Finally, Dr JN Nijm (Jonkoping, Sweden) reviewed the field of neutrophil-platelet aggregates in ACS. He showed original data on stable CAD patients showing that neutrophil-platelet aggregate numbers are increased with respect to a control group. However, controversial data was shown in some of the parameters associated to neutrophil cell function. Dr Nijm concluded that the clinical significance of neutrophil dysfunction in CAD remains to be elucidated. Furthermore, whether neutrophil-platelet aggregates are just markers or causal agents in the progression of CAD also remains to be determined.

This was a very stimulating session that presented new areas in which to invest our efforts in order to expand our understanding of clinical atherothrombosis.




Thrombus formation in acute coronary syndromes: what is new?
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.