Hyperlipidemia Could Activate Platelet and Induce the Production of Plasma Inflammatory Factors in Rabbits, Which Lead to Atherosclerosis

Abstract

Background: It had been proved by epidemiology and clinical trials that hypercholesterolemia (HC) and atherosclerosis (AS) had close relations. Lipid could take part in many pathological processes of the AS. Platelets played an important role in this process as an inflammatory mediator. We Chose Platelet aggregation maximum (PAG(M)) and plasma P-selectin as the index of platelet activation, try to explore the transfer of platelet activation and lymphocyte inflammatory reaction in atherosclerosis.Design: We set up the rabbit hyperlipidemia atherosclerosis model through 12 weeks' hyper lipid feeding. PAG(M), concentrations of plasma P-selectin, Interleukin (IL)- 6, IL-1β, tumor necrosis factor (TNF)-α and mRNA expression of these factors in the lymphocyte were measured at 0 week, 6th week and 12th week time point.Results: At the 6th week time point of the hyper lipid feeding, the rabbit had elevated PAG(M) (68.12%±4.73% vs. 62.67%±3.13%; P=0.002, n=20). The PAG(M) was maintained in the high level at 12th week time point (68.83%±3.35% vs. 62.67%±3.13%; P=0.001, n=20). At the 6th week time point of the hyper lipid feeding, the rabbit had elevated plasma P-selectin, IL-6, IL-1β and TNF-α (6th week vs. 0 week, n=20, P-selectin P=0.005, IL-6 P=0.000, IL-1β P=0.001, TNF-α P=0.001). The expressions of IL-6/mRNA, IL-1β/mRNA and TNF-α/mRNA in lymphocytes were elevated too (6th week vs. 0 week, n=20, IL-6/mRNA P=0.000, IL-1β/mRNA P=0.002, TNF-α/mRNA P=0.000). At the 12th week time point, all of the parameters were maintained in the high level, while there had no significant difference between 12th week time point and 6th week time point.Conclusion: Hyperlipidemia could activate platelet. Increased PAG(M) and plasma P-selectin represented the platelet activation. Hyperlipidemia could induce the production of plasma IL-6, IL-1β and TNF-α. The increased plasma IL-6, IL-1β and TNF-α were partly from the lymphocyte secretion because The IL-1β/mRNA, IL-6/mRNA and TNF-α/mRNA expression of lymphocyte elevated. So in rabbit hyperlipidemia atherosclerosis model, platelet activation and inflammatory factors increasing was the main mechanism, while the lymphocyte took part in the inflammatory process.