Monomeric C-reactive protein and local inflammatory reaction in the wall of the coronary arteries in patients with stable coronary artery disease

Aim. To study the phenotype of microvesicles circulating in the blood plasma of patients with stable coronary artery disease (CAD), carrying monomeric C-reactive protein (mCRP) on their surface, and to detect tissue accretions of mCRP in coronary artery of patients with CAD.

Material and methods. Blood samples obtained from 20 patients with stable CAD and from 7 healthy volunteers were examined. The phenotype of microvesicles of cell origin was studied by flow cytometry. Microparticles were identified by their level of binding to annexin-V, and exosomes by binding to the monoclonal antibodies to CD63. The accretion of mCRP in the coronary arteries’ walls was investigated by immunohistochemical analysis of their fragments obtained from 7 men during coronary endarterectomy surgery. Samples were stained with monoclonal antibodies to native CRP (nCRP) and mCRP.

Results. More than half of the mCRP-positive blood microparticles were CD45-positive. At the same time, the mCRP+/CD45+ microparticles were CD63 positive and annexin-V negative, which makes it possible to characterize them as exosomes secreted into the extracellular space by activated leukocytes. Microparticles of platelet and erythrocyte origin were mainly annexin-V positive. It was very weakly or not at all associated with antibodies to mCRP. The amount of blood mCRP+/CD45+ exosomes was significantly higher in patients with CAD (8749+2683 particles per μL, n=20) than in healthy people (1454+350 particles per μL, n=7 p=0,00). An analysis of coronary arteries’ material has shown that mCRP is found in atherosclerotic plaques, while intact arterial wall samples were mCRP negative.

Conclusion. An increase of exosomes carrying on their surface mCRP and characteristic leukocyte markers, as well as the appearance of mCRP in areas of atherosclerotic arterial wall lesions, in patients with CAD, may indicate the involvement of proinflammatory mCRP molecules in the pathogenesis of coronary atherosclerosis. Since exosomes are specific transporters of signaling molecules of the parent cells, it can be assumed that mCRP is transported to damaged areas by activated leukocytes.

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