Abstract:Aim To study the correlation between the antioxidantion of plasma high density lipoprotein (HDL) and circulating microRNA (miRNA). Methods Scavenger receptor group B type Ⅰ deficient (SR-BⅠ－/－) mice as dysfunctional HDL model mice were used to explore the changes of specific miRNA spectrum. From September 2020 to May 1,0 patients with coronary artery disease (CAD) were enrolled in the Department of Cardiology, Zhongnan Hospital of Wuhan University, non-CAD patients in the same period as control group, both groups with HDL cholesterol (HDLC) higher than 1.04 mmol/L. Results Compared with wild-type mice, the plasma miR-135a in SR-BⅠ－/－ mice decreased significantly. Plasma paraoxonase 1 (PON-1) activity decreased in CAD patients, PON-1 activity in control group was positively correlated with HDLC level, but not in CAD group. The plasma miR-135a level in CAD patients also decreased, and was positively correlated with PON-1 activity. In CAD group, the level of plasma miR-17 decreased significantly, and the levels of miR-223 and miR-760 increased significantly, but there was no correlation with HDLC level or plasma PON-1 activity. Conclusion The level of plasma miR-135a decreased significantly in CAD patients with high HDLC, and was positively correlated with PON-1 activity, which may be related to the antioxidant function of HDL.

Abstract:Aim To explore the correlation between plasma HDL function and coronary artery stenosis and plaque property in coronary artery disease (CAD) patients with normal HDLC levels (≥1.03 mmol/L). Methods 129 cases suspected CAD with normal HDLC levels in Yichang Hospital of Traditional Chinese Medicine from October 2015 to December 2017 were enrolled, and grouped according to the severity of coronary artery stenosis and plaque property by 64-slice spiral CT coronary angiography (CTA). Paraoxonase 1 (PON1) activity and HDL oxidation/antioxidant index were detected. Results Compared with non-CAD group, plasma HDLC level and PON1 activity were significantly decreased, and HDL oxidation/antioxidant index was increased in the CAD group, showing an oxidized state, while ApoAI level had no difference. Although there were no difference in HDLC and ApoAI levels, PON1 activity was gradually decreased and HDL oxidation/antioxidant index was increased, accompanying with increased stenosis of coronary artery. The data also showed that PON1 activity of calcified plaque group was higher than that of soft plaque group and mixed plaque group. There is a correlation between PON1 activity and HDLC, HDL oxidation/antioxidant index. Conclusion PON1 activity as an index of HDL function may be a potential biomarker for assessment of the plaque property and severity of CAD.

Abstract:The anti-oxidative and anti-inflammatory activities of high density lipoproteins （HDL） are largely due to the paraoxonase 1 （PON1） located on it. PON1 is mainly synthesized in the liver and secreted into the circulation, using very low density lipoprotein （VLDL） as a vehicle to bind with HDL, and transferred between in the HDL subclasses. PON1 possesses a higher activity through interacting with other protein components in HDL, and plays an important role for HDL structure and its anti-oxidative and anti-inflammatory activities. The change in quantity and activity of PON1 is associated with abnormal structure and the atherogenic “dysfunction” of HDL. In this review we summarize data on the role played by PON1 on HDL structure and function, focusing on the relationship between their binding and interaction and function of HDL.

Abstract:Aim To investigate the effects of probucol on high fat-high cholesterol(HFHC)diet-induced hyperlipidemia and oxidative stress in apo E deficient(apoE-/-)mice and genetic background C57BL/6J mice.Methods The hyperlipidemic mice were induced by feeding HFHC diet which was supplemented with 15%lard and 0.25% cholesterol.The levels of plasma lipids were determined by standard assays.The oxidative stress was evaluated by the serum levels of total antioxidant capacity(T-AOC),superoxide dismutase(SOD),and malonic dialdehyde(MDA)determined by commercially provided kits.The aortic atherosclerotic lesions were demonstrated by Sudan IV staining.Activity of paraoxonase 1(PON1)was assessed by modified Echersons method.Expression level of PON1 in liver was evaluated by semi-quantitative reverse-transcription-polymerase reaction(RT-PCR).Results HFHC diet elevated the levels of serum triglyceride(TG),total cholesterol(TC),low density lipoprotein-cholesterol(LDLC),and high density lipoprotein-cholesterol(HDLC).Probucol decreased the elevation of serum levels of lipids.In C57BL/6J mice,the levels of TG,TC,LDLC,and HDL-C lowered 41%,43%,44.8%,and 41.3%,respectively,compared with control group(P<0.05).In apo E-/-mice,decrease of 36.2%,28.2%,31.3%,and 33.9%,respectively,was observed versus apo E-/-control(P<0.05).Probucol treatment prevented the atherosclerotic lesion development in both C57BL/6J and apoE-/-mice.Compared with HFHC groups,the aorta lesions were significantly decreased by 61.1% in C57BL/6J mice and by 27.2% in apo E-/-mice(P<0.05),respectively,after treatment of probucol.Admi-nistration of probucol lowered the serum levels of MDA and oxLDL,and elevated the levels of serum T-AOC and SOD.The results also demonstrated a more significant increase of PON1 activity and expression level in C57BL/6J mice than in apo E-/-mice.Conclusion Probucol decreases the levels of serum lipids and alleviates the atherosclerotic lesions in HFHC diet-induced hyperlipidemic mice.Probucol may contribute to a significant decrease of the oxidative stress.The effects of probucol may be attenuated by apo E deficiency in mice.