The Effect Of Crystals On ABCA1Expression And Cholesterol Efflux Capacity In THP-1Monocyte

BackgroundCoronary heart disease (CHD) is a major threat to human health. The basic pathological foundation of CHD is atherosclerosis. The diamond gaps as a trace of cholesterol crystals often presented in the specimen of atherosclerosis plaques. Recent study revealed that minor cholesterol crystals could be phagocytosed by phagocytic cell and lysosome, then the lysosome ruptured and NLRP3inflammasome triggered by the released lysosome contents, subsequently upgraded IL-1β which promoted the inflammation of atherosclerosis. Gout arthritis is independent cardiac and coronary artery disease risk factors. Uric acid crystals are commonly found in the articular cavity in gout arthritis. The proinflammatory factor IL-1β was also upgraded by uric acid crystals via NLRP3inflammasome. ATP binding cassette transportor A1(ABCA1) facilitate the efflux of cholesterol from cells, which is protective to atherosclerosis. The anti-inflammation property of ABCA1and cholesterol efflux may also be compromised under the condition of inflammation. In conclusion, we suspect that crystals may accelerate atherosclerosis and increase gout associated cardiac risk though impaired ABCA1and cholesterol efflux.ObjectiveExplore the effect of crystals on ABCAl expression and cholesterol efflux in THP-1monocyte.MethodsTHP-1monocyte were treated with low cholesterol crystal(0.5mg/ml), high cholesterol crystal(2.5mg/ml), uric acid crystal(1mg/ml) and oxidized low density lipoprotein (ox-LDL), respectively. The untreated cells were used as control group. After24hours, the relative gene and protein expression of ABCA1were measured by real-time polymerase chain reaction (PCR) and Western Blot, respectively. The efflux rates of3H-cholesterol in THP-1monocyte were detected by means of liquid scintillation counter.Results1compared with the control group, gene and protein expression of ABCA1of THP-1cell were significantly down-regulated in the low cholesterol crystal(0.5mg/ml) intervention group(P<0.05), while the cholesterol efflux rates form monocyte were also decreased(P>0.05).2compared with the control group, gene and protein expression of ABCA1of THP-1cell were significantly down-regulated in the uric acid crystal(0.5mg/ml) intervention group(P<0.05), while the cholesterol efflux rates from monocyte were also decreased(P>0.05).3compared with the control group, gene and protein expression of ABCA1of THP-1cell were significantly up-regulated in the high cholesterol crystal(0.5mg/ml) and ox-LDL intervention group(P<0.05), while the cholesterol efflux rates form monocyte were also increased significantly(P<0.05).ConclusionsABCA1expression and cholesterol efflux were changed diversely on the effect of different type and concentration of crystals, thus crystals may promote the progression atherosclerosis or make compensation effect.