Abstract
The contemporary theory of the inflammatory-immunological pathomechanism of atherosclerosis includes the participation of interleukin-1β (Il), Il-6, Il-10, Il-12, RANTES, and homocysteine in this process. The knowledge on the direct effect of hyperhomocysteinemia on inflammatory-state-related atherosclerosis is rather scarce. Our study is the first to account for the effects of homocysteine on the secretion of Il-10 and RANTES in vitro conditions. For this purpose, human mitogen-stimulated peripheral blood mononuclear cells (PBMNCs) were cultured in vitro and exposed to homocysteine at high concentrations. Subsequently, the concentrations of cytokines were assayed in the cell culture supernatant using flow cytofluorimetry. It has been shown that, in the presence of homocysteine, the secretion of IL-1, IL-6 and RANTES by PBMNCs was increased, whereas IL-10 concentration was significantly lower than that of the supernatant derived from a mitogen-stimulated cell culture without homocysteine. The secretion of Il-12 by PBMNCs exposed exclusively to mitogen, did not differ from homologous cells also treated with homocysteine. Therefore, in our opinion, high-concentration homocysteine affects the progression of atherosclerosis by increasing the secretion of proinflammatory cytokines secreted by PBMNCs, such as Il-1β, Il-6, RANTES, and by attenuating the secretion of Il-10.
Highlights
Progressive atherosclerosis is a major causative factor in ischemic heart disease, myocardial infarction, stroke and other atherosclerosis-related complications [1]
It should be emphasized that an increased secretion of Il-1β, Il-6, Il-12 and RANTES chemokines and, at the same time, a reduced secretion of anti-inflammatory Il-10 due to hypercholesterolaemia, oxidative stress and hyperglycaemia, resulted in vascular wall damage and the progression of atherosclerosis [3,4,5]
6T0h0 e secretion of Il-12 by cells coming from healthy individuals exposed exclusively to mitogen did not differ from homologous cells that were treated with homocysteine (Figu5r0e0 5)
Summary
Progressive atherosclerosis is a major causative factor in ischemic heart disease, myocardial infarction, stroke and other atherosclerosis-related complications [1]. It should be emphasized that an increased secretion of Il-1β, Il-6, Il-12 and RANTES chemokines and, at the same time, a reduced secretion of anti-inflammatory Il-10 due to hypercholesterolaemia, oxidative stress and hyperglycaemia, resulted in vascular wall damage and the progression of atherosclerosis [3,4,5]. 6T0h0 e secretion of Il-12 by cells coming from healthy individuals exposed exclusively to mitogen did not differ from homologous cells that were treated with homocysteine (Figu5r0e0 5). Il-1β, Il-6, Il-12, Il-10 and RANTES expression in cell suspension with mitogen (Flow Cytometry raw data for a single patient). Homocysteine stimulates the secretion of interleukin 1β, interleukin 6 and RANTES chemokines These studies provide direct evidence for the close relationship between high homocysteine levels in the blood and the intensity of inflammation. The Flex Set test used for the study was focused on the Il-12p70 evaluation, but not on p40 subunit
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