Human ApoA-I Overexpression Diminishes LPS-induced Systemic Inflammation And Multiple Organ Damage In Mice

The present study was focused on the following two specific aims:1.To establish human ApoA-I overexpressing mice model,2.To investigate the protective effect of human ApoA-I over-expression against LPS-induced systemic inflammation and multiple organ damage in mice.Recombinant adenovirus vector carrying human apolipoprotein A-I(ApoA-I) gene (AdV-AI) was constructed,amplified and purified.AdV-AI was infused intravenously into 6-week BALB/c mice to establish a human ApoA-I over-expressing model. Establish of such model was confirmed by both mRNA level examination(RT-PCR) and protein level examination.Based on the human ApoA-I overexpressing model,following alterations were assayed in order to find the protective effect of ApoA-I against LPS-induced systemic inflammation and multiple organ damage:1.Level of lipid(HDL-cholesterol,total cholesterol,TG) in serum2.Size of HDL particles in serum3.TNF-α,IL-6,IL-1βlevels in serum and bronchoalverolar lavage(BAL) fluid4.CD14 level in liver and lung5.CK and CRE levels in serum6.Histopathological examination of lung and kidney tissuesThe over-expression of ApoA-I resulted in following changes:1.over expression of human ApoA-I level and no change of mouse ApoA-I in serum of AdV-AI mice2.significant increases of serum total cholesterol,HDL cholesterol and triglycerides in AdV-AI mice(P<0.01,P<0.01 and P<0.05,respectively)3.the humanized HDL was appeared in serum of AdV-AI mice4.significant inhibition of LPS-induced increments of TNF-α,IL-6,IL-1βlevels in serum(P<0.01,P<0.05 and P<0.05,respectively) and in BAL fluid(P <0.05,respectively)5.significant reduction of LPS-induced increments of CD14 mRNA expression in liver and lung(P<0.05 and P<0.01,respectively)6.significant inhibition of LPS-induced increments of serum CK and CRE(P< 0.05,respectively)7.attenuation of LPS-induced acute injury in lung and kidney tissuesConclusions:1.Human ApoA-I overexpression leads to the changes of serum lipids and appearance of humanized HDL in mice.2.Human ApoA-I overexpression plays a protective effect against LPS-induced systemic inflammation and multiple organ damage in mice.3.The antiinflammatory effect of ApoA-I might attribute partly to the suppression of inflammatory cytokines release and reduction of CD14 expression.