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Immunomodulatory functions of enzymes matrix metalloproteinases, innate immune cells, CD 68 and heat shock protein 70 in the ethiopathogenesis of atherosclerosis

Background: Atherosclerosis represents an inflammatory, autoimmune, and chronic metabolic disorder of the vessel wall, with genetic and environmental factors in its etiopathogenesis. Oxidized low-density lipoprotein (oxLDL) in vitro can contribute to Treg/Th17 balance in the periphery inducing the apoptosis of regulatory T cells (Tregs) and the proliferation of Th 17. Three proteins are identified as autoantigens: heat shock proteins (HSPs), oxidized low density lipoprotein (oxLDL) and beta 2 glycoprotein 1 (b2GP1). The matrix metalloproteinases (MMPs) play a key role in angiogenesis with migration and/ or invasion of endothelial cells in surrounding stroma and tissues. The CD68 molecule have an ability to bind oxLDL and points a possible role in atherogenesis and intracellular lipid accumulation. The aim of this study: To examine the interactions between the enzyme matrix metalloproteinases, the innate immune cells and CD68+cells of patients with mild atherosclerosis (A patients) and with carotid arteries stenosis (CAS patients) who were undergoing the surgical procedure. Patients and methods: Patients were selected from a stratified sample of the population of adult patients of both sexes with diagnosed atherosclerotic changes in medium and large- sized arteries. We used the method of enzyme immunoassay (ELISA) for the investigation of the concentration of enzyme MMPs in urine. Innate immunity was analyzed by flow cytometric method. Immunohistochemically expression of the heat shock 70 (hsp 70) protein on paraffinic atherosclerotic alterations of carotid arteries were done. Results: patients with developed atherosclerosis (CAS group) had statistically significant increases in MMP 2 and 9 enzyme urine levels. In the peripheral blood had statistically significant increases in CD68 + molecule, NKT cells and statistically significant decrease in Tregs. The elevated values of NKT cells correlate with the elevated values of enzymes MMP 2 and 9 and are down regulated with the diminished Tregs values. Our data showed a rise in the expression of heat shock protein 70 in atheroscleroticmodified carotid arteries. Conclusion: High concentration of MMP 2 and 9 enzymes followed by diminished values of Tregs in atherosclerotic patients highlights the importance of regulatory T immunity in atherosclerotic etiopathogenesis and indicated determination of MMPs as an easy markers for the monitoring of the development of atherosclerosis. Heat shock proteins (HSPs) act as autoantigens and stimulate cellular and humoral immune responses. Acknowledgement: This work is supported by grants from the University of Rijeka (18-220, 18-146 and 18-301)

Atherosclerosis ; CD 68 ; Ethiopathogenesis ; Heat shock protein ; Innate immune ; Heat shock protein 70 ; Matrix metalloproteinases

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