Effect And Mechanisms Of Oligodeoxynucleotides Inhibit Atherosclerosis In Rats

Abundant data link hypercholesterolaemia to atherogenesis. However, only recently have we appreciated that inflammatory mechanisms couple dyslipidaemia to atheroma formation. Leukocyte recruitment and expression of pro-inflammatory cytokines characterize early atherogenesis, and malfunction of inflammatory mediators mutes atheroma formation in mice. Moreover, inflammatory pathways promote thrombosis, a late and dreaded complication of atherosclerosis responsible for myocardial infarctions and most strokes. T cells are involved in the lesions of atherosclerosis. During the process of atherosclerosis, cytokines and adhesion molecular including IFN-γ, TNF-α, VCAM-1 and ICAM-1 seem to play a central role. Therefore, inhibition of expression of IFN-y, TNF-a, VCAM-1 and ICAM-1 in process of atherosclerosis may be new therapeutic target.Inhibitory oligodeoxynucleotides (ODNs), an artificial single-stranded DNA molecule, could antagonism to activation of TLRs. Recent studies demonstrate that inhibitory ODNs show a promise to develop an agent for the treatment of diseases associated with Toll-like receptor activation. In all kinds of ODNs, ODN with G rich is optimal to treat diseases caused by excessive secretion of IFN-y. ODN 2114 is a protype of G-rich ODNs.Our studies demonstrate ODN2114 can inhibit atherogenesis and expression of inflammation cytokines and adhesion molecules in rats. Therefore, ODN2114 maybe have potential to become prophylactic and therapeutic vaccine to atherosclerosis.