Abstract
BackgroundAtherosclerosis (AS) is a chronic inflammatory disease. The role of the immune system in the etiology of the disease, particularly T cells, has been widely studied and is well established. T cell activation directly regulates co-signaling molecules present in immune synapses. Targeting one or several of these co-signaling molecules can inhibit T cell-mediated inflammation and delay or reduce AS. In recent years, this strategy has increasingly become a research focus. As such, we explored the role and therapeutic potential of the T cell co-stimulatory molecule inducible co-stimulatory (ICOS) in AS.MethodsWe compared the expression of ICOS in early AS lesions occurring in ApoE-deficient (ApoE-KO) rats fed a fat-diet and wild type (WT) rats fed the same diet. Eight-week old ApoE-KO and WT rats [ApoE-KO(0) and WT(0)] were fed a high-fat diet for 16 weeks [ApoE-KO(16) and WT(16)]. ICOS expression in aortic tissues was analyzed by quantitative real-time PCR, western blot, and confocal microscopy. The effect of ICOS overexpression in a transfected human T cell line on the phagocytosis and proliferation of co-cultured human aortic smooth muscle cells (HASMCs) was studied in vitro.ResultsCompared with WT(0), ApoE-KO(0), and WT(16) rats, ICOS expression in ApoE-KO(16) rats was significantly down-regulated both at the mRNA and protein levels. In vitro experiments indicated that ICOS overexpression reduces phagocytosis and proliferation by HASMCs, and may therefore produce an anti-atherosclerotic effect.ConclusionsThe immune synaptic co-signaling molecule ICOS has an anti-atherosclerotic effect through inhibition of HASMC phagocytosis and proliferation, and can be used to delay plaque formation during the early stages of AS.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.