Abstract:Aim To investigate the relationship between small and dense low density lipoprotein cholesterol (sdLDLC) and atherogenic index of plasma (AIP) in patients with coronary heart disease (CHD). Methods A total of 525 patients admitted to our hospital due to chest pain and chest tightness from September 2019 to June 2020 and suspected CHD underwent coronary angiography were retrospectively collected as the research subjects. According to coronary angiography results, they were divided into CHD group (n＝422) and non-CHD group (n＝103). At the same time, they were divided into three groups according to AIP tertiles:AIP≤－0.056 group (n＝176), －0.056＜AIP＜0.208 group (n＝175), AIP≥0.208 group (n＝174). Each lipid index was measured and AIP was calculated. sdLDLC and AIP levels were compared between CHD group and non-CHD group. Influencing factors for AIP and risk factors for CHD were analyzed. Results The sdLDLC, AIP, low density lipoprotein (LDL) subtype LDL3, LDL4 in CHD group were significantly higher than those in non-CHD group, and the LDL1, high density lipoprotein cholesterol in CHD group were significantly lower than those in non-CHD group (P＜0.05). With the increase of AIP, sdLDLC and LDL4 increased significantly, while LDL1 and LDL2 decreased significantly (P＜0.001). Multiple linear regression analysis showed that sdLDLC and history of hypertension were independent influencing factors of AIP (P＜0.05). Multivariate Logistic regression analysis showed that sdLDLC and AIP were independent risk factors for CHD (P＜0.05). Conclusion There is a significant positive correlation between sdLDLC and AIP in CHD patients, and sdLDLC and AIP are independent risk factors for CHD.

Abstract:Aim To explore the effect of Curcumin on that inducible degrader of the low density lipoprotein receptor (IDOL) regulating the uptake of low density lipoprotein cholesterol (LDLC) of hepatocytes. Methods HepG2 and LO2 cells (two kinds of hepatocytes) were infected with the constructed overexpression or RNA-interference IDOL (OE/RNAi-IDOL) lentivirus. The efficiency of the lentiviral infection experiment was evaluated by fluorescence microscopy. The expression of IDOL and low density lipoprotein receptor (LDLR) proteins was detected by Western blot. After HepG2 and LO2 cells were treated with Curcumin for 24 hours, intracellular lipid droplets were determined by red oil O staining; cholesterol content was detected by using cholesterol testing kits; the uptake of LDLC by hepatocytes was detected by DiI-LDL uptake experiment; LDLR abundances of hepatocytes surfaces were determined by immune flow cytometry. Results Compared with white light view, the phenomenon of the green fluorescence was observed both in HepG2 and LO2 cells infected by OE-IDOL and RNAi-IDOL lentivirus; Western blot results showed that both in HepG2 and LO2 cells infected by RNAi-IDOL-2 lentivirus, IDOL protein expression were decreased, while LDLR expression was increased (P＜0.01); on the contrary, in HepG2 and LO2 cells infected by OE-IDOL lentivirus, IDOL protein expression was increased, while LDLR expression was decreased, the above results indicated that both HepG2 and LO2 cells infected by OE/RNAi-IDOL lentivirus had been acquired. Compared with the control group of HepG2 and LO2 cells without any treatment, after 25 μmol/L Curcumin treatment for 24 hours in the OE/RNAi-IDOL lentivirus infected cells, both the intracellular lipid droplet content and relative cholesterol content were increased in the treatment group (P＜0.01), meanwhile the uptake LDLC ability and cell surface LDLR abundances of hepatocytes were also enhanced (P＜0.01), the same trend was also observed in the results of Rosuvastatin treatment group. Conclusion The levels of IDOL protein in liver cells were down-regulated by Curcumin, which further promotes the uptake of LDLC of liver cells.

Abstract:Aim To observe whether the effect of curcumin on lipid uptake of human hepatoma cell line HepG2 is related to kinesin family member 16B (KIF16B), and to explore the lipid-lowering mechanism of curcumin. Methods (1)The HepG2 cells cultured in vitro were divided into control group (curcumin concentration was 0) and 0,0, 40 μmol/L curcumin treatment groups, and CCK8 method was used to detect cell viability to determine the appropriate concentration of curcumin. (2)The HepG2 cells cultured in vitro were divided into blank control group, negative control group, rosuvastatin (positive drug) group and curcumin group. Cholesterol detection kit was used to detect the content of cholesterol in HepG2 cells; The uptake of DiI-labeled low density lipoprotein (DiI-LDL) was observed by fluorescence microscope; The protein expressions of KIF16B and low density lipoprotein receptor (LDLR) were detected by Western blot; The fluorescence co-localization of KIF16B and LDLR was observed by laser confocal microscope. Results 25 μmol/L curcumin did not affect the growth of HepG2 cells. Compared with the negative control group, the levels of total cholesterol and free cholesterol in HepG2 cells were significantly increased, the uptake of DiI-LDL by cells was significantly increased, the expressions of KIF16B and LDLR proteins in the cells were significantly increased, and the fluorescence co-localization of KIF16B and LDLR proteins in the cells was significantly increased in the curcumin group (P＜0.05). Conclusion The increase of LDL lipid uptake and LDLR expression caused by curcumin acting on HepG2 cells is related to the interaction between KIF16B and LDLR.

Abstract:Aim To explore the correlation between lipid deposition index and atherosclerosis of coronary heart disease (CHD) and optimize the best index to provide reference for clinical diagnosis and treatment. Methods 231 patients who underwent coronary angiography from January 2018 to February 2019 were selected. According to the results of coronary angiography, the patients were divided into three groups:non-CHD group (n＝75), CHD non-intervention group (n＝80), and CHD intervention group (n＝76). Routine biochemistry and full set of blood lipid indexes were detected by automatic biochemical analyzer. The correlation between lipid deposition index and the degree of atherosclerosis was analyzed. ROC curve was used to analyze the specificity and sensitivity of lipid deposition index in predicting CHD.Results There were significant differences in age, body mass index, total cholesterol, low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol, apolipoprotein B, apolipoprotein A1, homocysteine (Hcy), C-reactive protein (CRP) and cardiac troponin I among the three groups (P＜0.05). Logistic regression analysis showed that lipid deposition index A,Dü and E were positively correlated with the degree of atherosclerosis in CHD (P＜0.05), among which the correlation of lipid deposition index E composed of LDLC×age×Hcy×CRP was the highest. ROC curve analysis showed that the area under curve of lipid deposition index E was 0.618, the specificity was 0.911, and the sensitivity was 0.767, which was the highest in predicting CHD. Conclusion There is a significant positive correlation between lipid deposition index E and the degree of atherosclerosis in CHD. Lipid deposition index E can highly predict the degree of coronary artery lesions.

Abstract:Dyslipidemia is a major risk factor for cardiovascular disease, especially elevated low density lipoprotein cholesterol (LDLC) significantly increases the incidence of atherosclerotic cardiovascular disease (ASCVD). Statins have shown to be effective in reducing serum LDLC, thereby reducing the risk of ASCVD. However, in the course of clinical application of statins, more and more studies show that statins have drug resistance. Studies have shown that statin resistance is mainly affected by drug absorption, transport, metabolism and drug action itself. Intensive study of statin resistance can provide theoretical basis for further revealing the action mechanism of statins, and hopefully provide a target for the development of new lipid-lowering drugs.

Abstract:Aim To investigate the effect of ezetimibe on hepatic low density lipoprotein cholesterol (LDLC) uptake and its mechanism. Methods The hyperlipidemia model mice had intragastric administration of 5 mg/(kg·d) ezetimibe. After four months, the contents of total cholesterol (TC), LDLC and high density lipoprotein cholesterol (HDLC) were measured in the blood of mice, and liver tissue morphology was observed by HE staining. HepG2 cells were incubated with ezetimibe (30 μmol/L) and low density lipoprotein (25 mg/L) for 24 hours. The distribution of lipid droplets in cells was observed by oil red O staining. Enzymatic method was used to detect the contents of intracellular TC, free cholesterol (FC) and cholesteryl ester (CE). The uptake of LDLC in cells was detected by DiI-LDL. Real-time fluorescence quantitative PCR and Western blot were used to detect sterol regulatory element binding protein-2 (SREBP-2) and low density lipoprotein receptor (LDLR) expressions at mRNA and protein level, respectively. LDLR content in the hepatic cell membrane was detected by flow cytometry. Results Ezetimibe reduced the content of TC and LDLC in the plasma of mice, increased the content of HDLC and reduced the lipid deposition in liver. Ezetimibe enhanced the ability of HepG2 cells to take LDLC, and promoted the transformation of FC into CE. Ezetimibe up-regulated the expressions of SREBP-2 and LDLR in HepG2 cells, and increased the distribution of LDLR on the cell membrane. Conclusion Ezetimibe can promote the uptake of LDLC in liver cells by up-regulation of SREBP-2 and LDLR.

Abstract:Aim To investigate the change of serum small and dense low density lipoprotein cholesterol (sdLDLC) level in patients with coronary heart disease (CHD) after lipid-lowering therapy. Methods Blood samples were collected from 1065 patients with CHD and 469 healthy controls from March to July 2016. Serum low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC) and sdLDLC levels were measured by direct assay, and serum triglyceride (TG) and total cholesterol (TC) levels were measured by enzyme method. The reference interval of the healthy control group was established. According to the serum LDLC level of CHD patients after lipid-lowering therapy, lipid-lowering LDLC standard group and intensive lipid-lowering LDLC standard group were determined. The blood lipid indexes were compared in each group, and the changes of sdLDLC level and sdLDLC/LDLC ratio were analyzed and compared. Results (1)After lipid-lowering therapy, CHD group compared with the healthy control group, there were significant differences in TG, HDLC and sdLDLC/LDLC ratio between the two groups (P＜0.05), and there were no significant differences in the levels of TC, LDLC and sdLDLC between the two groups (P＞0.05). (2)Compared with the healthy control group, the sdLDLC/LDLC ratio increased in lipid-lowering LDLC standard group (P＜0.05), and there was no significant difference in sdLDLC level between the two groups (P＞0.05). Among the patients who had reached the standard of lipid-lowering, the sdLDLC level of 2.3% CHD patients and the sdLDLC/LDLC ratio of 7.7% CHD patients were higher than the reference interval established by this study. (3)Compared with the healthy control group, SdLDLC level reduced and sdLDLC/LDLC ratio increased in intensive lipid-lowering LDLC standard group (P＜0.05). Among the patients who had reached the standard of intensive lipid-lowering, the sdLDLC level of 0.8% CHD patients and the sdLDLC/LDLC ratio of 15.3% CHD patients were higher than the reference interval established by this study. ConclusionsIn the lipid-lowering therapy and intensive lipid-lowering therapy for CHD patients, the changes of serum sdLDLC level and sdLDLC/LDLC ratio are of great significance for risk analysis of residual cardiovascular events. Lowering sdLDLC level may be one of the important indicators that ultimately reduce the risk of CHD.

Abstract:Aim To investigate the relationship between serum proprotein convertase subtilisin/kexin type 9 (PCSK9) and small and dense low density lipoprotein cholesterol (sdLDLC) in patients with coronary heart disease (CHD). Methods From March 2014 to December 2014 in the first hospital of Shanxi Medical University, 100 patients with CHD diagnosed by coronary angiography were collected as CHD group, and 67 healthy subjects were served as control group. Lipoprint lipoprotein analyzer was used to measure the LDLC particle size, sdLDLC particle number and the percentage of sdLDLC in LDLC (sdLDLC percentage). Serum PCSK9 level was detected by enzyme-linked immunosorbent assay. Results Compared with the control group, LDLC particle size decreased (264.07±6.78 vs. 267.37±5.15, P＜0.01), sdLDLC particle number increased (5.0±9.5 vs. 4.0±5.0, P＜0.05), sdLDLC percentage increased (5.95%±10.50% vs. 3.70%±5.85%, P＜0.01) in the CHD group. The serum PCSK9 level in CHD group was significantly higher than that in control group (15.48 μg/L vs. 14.95 μg/L, U＝－2.74, P＝0.006). In the CHD group, serum PCSK9 level was positively correlated with sdLDLC percentage and LDLC (r＝0.212, P＝0.034; r＝0.202, P＝0.032). Conclusion Serum PCSK9 level is positively correlated with sdLDLC percentage in patients with CHD, and the inhibition of PCSK9 can prevent CHD.

Abstract:Aim To investigate the present prevalence and risk factors of high LDLC among middle and aged population in urban and rural areas of Chengdu,and to lay the foundation for the future of hyperlipidemia prevention. Methods To investigate the prevalence of high LDLC and influential factors in Chengdu. 5230 persons of 40～79 years old in the urban and rural communities were investigated . Data were collected through questionnaire,physical examination,and laboratory tests. Results The prevalence rate of elevated LDLC among middle-aged and elderly people was 2.18% in Chengdu and the standardized prevalence rate was 2.03%. In 40～74 years old ,the prevalence of elevated LDLC increased gradually with age. The prevalence rate decreased slightly after 75 years old. There was no difference in the prevalence of urban and rural areas. The risk factors of high LDLC in middle-aged and elderly male population in Chengdu area were age and diabetes. Moderate drinking was a protective factor. Risk factors of elevated LDLC in middle-aged and elderly women were rmacrosomia,abdominal obesity and diabetes,protective factors were moderate alcohol consumption and physical exercise. Conclusion Prevalence of elevated LDLC among middle-aged and elderly people in urban and rural Chengdu is low. It is lower than the national level. To decrease prevalence of high low density lipoprotein cholesterol is of great significance for the prevention and treatment of coronary heart disease. Prevention of diabetes,moderate drinking and physical exercise may have positive significance in the prevention of elevated LDLC.

Abstract:Aim To determine whether small, dense low density lipoprotein cholesterol （sdLDLC） affects common carotid artery intima-media thickness （CCA-IMT） or not. Methods 130 patients who had dyslipidemia, diabetes mellitus, hypertension, or smokers participated in this experiment. SdLDLC was collected from automatic analyzer, and CCA-IMT analysis datas were obtained from high-resolution B-mode ultrasound. Results The sdLDLC in CCA-IMT thickening group was significantly higher than that in CCA-IMT normal group （43.97 ± 11.35 mg/dL vs 26.01 ± 7.62 mg/dL, P＜0.001）. The positive association of CCA-IMT with sdLDLC was significant （r0.857, P＜0001）. Conclusions This result indicates that sdLDLC was the best marker of CCA-IMT and suggests that quantitative measurement of sdLDLC provides useful information for the risk assessment of CCA-IMT.