Efficacy and safety of ongericimab given by prefilled syringe or autoinjector in primary hypercholesterolemia and mixed hyperlipidemia.

BACKGROUND AND AIMS: Limited evidence exist regarding the association between ongericimab, a novel recombinant humanized anti-PCSK9 monoclonal antibody, and primary hypercholesterolemia and mixed dyslipidemia. This study aimed to evaluate the efficacy and safety of ongericimab administered by prefilled syringe (PFS) or autoinjector (AI) in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia on stable optimized lipid-lowering therapy. METHODS AND RESULTS: A total of 255 patients on stable optimized lipid-lowering therapy were randomized in a 2:1:2:1 ratio to receive PFS for the subcutaneous injection of ongericimab 150 mg every 2 weeks (Q2W) or a matching placebo, or AI for the subcutaneous injection of ongericimab 150 mg Q2W or a matching placebo. The primary efficacy endpoint was the percent change in low-density lipoprotein cholesterol (LDL-C) levels from baseline to week 12. Safety was also evaluated. At week 12, the least squares mean percent changes were -72.7% (3.9%) for PFS and -71.1% (3.8%) for AI (all P < 0.001) compared to respective matching placebo groups. Beneficial effects were also seen for all secondary lipid parameters, notably with robust reduction in Lp (a). Treatment-emergent adverse events (TEAEs) and serious AEs with ongericimab were reported in 46.2% and 2.4% of patients, compared to 44.2% and 3.5% with placebo. CONCLUSION: In Chinese patients with primary hypercholesterolemia and mixed dyslipidemia, a 12-week treatment regimen with ongericimab administered by PFS or AI significantly reduced LDL-C and other lipid parameters, proving to be safe and well tolerated. Patients experienced consistent effects from PFS or AI devices. CLINICAL TRIAL REGISTRATION: CTR20220027; January 11, 2022; http://www.chinadrugtrials.org.cn/index.html.

Potential Regulatory Role of lncRNA-miRNA-mRNA in Coronary Artery Disease (CAD).

Coronary artery disease (CAD) is a high-incidence of heart disease. We aimed to identify potential biomarkers linked to the progression of CAD using multiple sets of data mining analysis methods. The long noncoding RNA (lncRNA) + messenger RNA (mRNA) data set GSE113079 and microRNA (miRNA) data set GSE28858 were downloaded from Gene Expression Omnibus. After data preprocessing, differentially expressed mRNA, lncRNA, and miRNA were identified using limma software. In addition, weighted gene co-expression network analysis (WGCNA) was used for the construction and screening of modules related to disease states. Besides, key mRNAs and lncRNAs were extracted for protein-protein interaction (PPI) network construction and lncRNA-mRNA co-expression analysis. Additionally, the final integration resulted in the lncRNA-miRNA-mRNA relationship pairs (competing endogenous RNA (ceRNA) network). Finally, CTD 2020 update database was used for the verification of the expression level of the candidate genes. A total of 1319 differentially expressed mRNAs and 1983 lncRNAs were screened. After WGCNA, a total of 234 mRNAs and 546 lncRNAs were identified. A PPI network including 127 mRNA corresponding proteins was constructed. The ceRNA network included 24 up-regulated lncRNAs, 16 down-regulated miRNAs, and 42 up-regulated mRNAs. Through the validation of CTD 2020 update database, 21 CAD related mRNAs, and four important ceRNAs those may be participated in the pathogenesis of CAD were obtained. In this study, through multiple sets of data mining methods, the regulatory relationship of lncRNA, miRNA, and mRNA was comprehensively analyzed, and the important role of lncRNA-miRNA-mRNA in the pathogenesis of CAD was emphasized.

miR-122 promotes hepatic lipogenesis via inhibiting the LKB1/AMPK pathway by targeting Sirt1 in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common hepatic disease with an increasing prevalence but an unclear aetiology. This study aimed to investigate the functional implications of microRNA-122 (miR-122) in the pathogenesis of NAFLD and the possible molecular mechanisms. METHODS: Both in vitro and in vivo models of NAFLD were generated by treating HepG2 and Huh-7 cells with free fatty acids (FFA) and by feeding mice a high-fat diet (HFD), respectively. HE and Oil Red O staining were used to examine liver tissue morphology and lipid deposition, respectively. Immunohistochemical (IHC) staining was used to examine Sirt1 expression in liver tissues. qRT-PCR and Western blotting were employed to measure the expression of miR-122, Sirt1, and proteins involved in lipogenesis and the AMPK pathway. Enzyme-linked immunosorbent assay (ELISA) was used to quantify triglyceride (TG) levels in HepG2 and Huh-7 cells and in liver tissues. The interaction between miR-122 and the Sirt1 gene was further examined by a dual luciferase reporter assay and RNA-immunoprecipitation (RIP). RESULTS: NAFLD hepatic tissues and FFA-treated HepG2 and Huh-7 cells presented excess lipid production and TG secretion, accompanied by miR-122 upregulation, Sirt1 downregulation, and potentiated lipogenesis-related genes. miR-122 suppressed Sirt1 expression via binding to its 3'-untranslated region (UTR). Knockdown of miR-122 effectively mitigated excessive lipid production and suppressed the expression of lipogenic genes in FFA-treated HepG2 and Huh-7 cells via upregulating Sirt1. Furthermore, miR-122 knockdown activated the LKB1/AMPK signalling pathway. CONCLUSION: The inhibition of miR-122 protects hepatocytes from lipid metabolic disorders such as NAFLD and suppresses lipogenesis via elevating Sirt1 and activating the AMPK pathway. These data support miR-122 as a promising biomarker and drug target for NAFLD.

Inhibition of Soluble Epoxide Hydrolase in Macrophages Ameliorates the Formation of Foam Cells　- Role of Heme Oxygenase-1.

BACKGROUND: Accumulation of foam cells in the neointima represents an early stage of atherosclerosis. 1-trifluoromethoxyphenyl-3-(1-propionylpiperidine-4-yl) urea (TPPU), a novel soluble epoxide hydrolase inhibitor (sEHi), effectively elevates epoxyeicosatrienoic acid (EET) levels. The effects of EETs on macrophages foam cells formation are poorly understood.Methods and Results:Incubation of foam cells with TPPU markedly ameliorate cholesterol deposition in oxidized low-density lipoprotein (oxLDL)-loaded macrophages by increasing the levels of EETs. Notably, TPPU treatment significantly inhibits oxLDL internalization and promotes cholesterol efflux. The elevation of EETs results in a decrease of class A scavenger receptor (SR-A) expression via downregulation of activator protein 1 (AP-1) expression. Additionally, TPPU selectively increases protein but not the mRNA level of ATP-binding cassette transporter A1 (ABCA1) through the reduction of calpain activity that stabilizes the protein. Moreover, TPPU treatment reduces the cholesterol content of macrophages and inhibits atherosclerotic plaque formation in apolipoprotein E-deficient mice. These changes induced by TPPU are dependent on heme oxygenase-1 (HO-1) activation. CONCLUSIONS: The present study findings elucidate a precise mechanism of regulating cholesterol uptake and efflux in macrophages, which involves the prevention of atherogenesis by increasing the levels of EETs with TPPU.

Emerging evidences for the opposite role of apolipoprotein C3 and apolipoprotein A5 in lipid metabolism and coronary artery disease.

Apolipoprotein C3 (apoC3) and apolipoprotein A5 (apoA5), encoded by APOA1/C3/A4/A5 gene cluster, are two critical regulators of plasma triglyceride (TG) metabolism. Deficiency of apoC3 or apoA5 led to significant decreased or increased plasma TG levels, respectively. Recent studies indicated apoC3 and apoA5 also played roles in plasma remnant cholesterol, high density lipoprotein (HDL) and hepatic TG metabolisms. Moreover, large scale population genetic studies indicated that loss of function mutations in APOC3 and APOA5 gene conferred decreased and increased risk of coronary artery disease (CAD), respectively. This manuscript mainly reviewed existing evidences suggesting the opposite role of apoC3 and apoA5 in lipid metabolism and CAD risk, and discussed the potential correlation between these two apolipoproteins.

Determination of optimal cut-off points after a high-fat meal corresponding to fasting elevations of triglyceride and remnant cholesterol in Chinese subjects.

BACKGROUND: Postprandial high triglyceride (HTG), marking elevated level of remnant cholesterol (RC), is an independent risk factor of coronary heart disease (CHD). The postprandial cut-off points for HTG and high RC (HRC) after a daily meal are recommended as 2.0 mmol/L and 0.9 mmol/L, respectively, by the European Atherosclerosis Society (EAS), while those after a high-fat meal in Chinese subjects were not explored. METHODS: Ninety subjects, including 60 CHD patients (CHD group) and 30 non-CHD controls (CON group), were enrolled in this study. Serum levels of blood lipids, including calculated RC, were monitored at 0, 2, 4 and 6 h after a high-fat meal with 800 kcal and 50 g fat. Analysis of c-statistic was used to determine the cut-off points for postprandial HTG and HRC. RESULTS: Postprandial levels of triglyceride (TG) and RC significantly increased and peaked at 4 h after a high-fat meal in two groups, although those in CHD group were significantly higher (P < 0.05). The optimal cut-off point to predict HTG at 4 h corresponding to fasting TG ≥ 1.7 mmol/L was 3.12 mmol/L, and that to predict HRC at 4 h corresponding to fasting RC ≥ 0.8 mmol/L was 1.36 mmol/L. According to the new cut-off points, the omissive diagnosis rates of postprandial HTG and HRC decreased obviously. CONCLUSION: The cut-off points of postprandial HTG and HRC in Chinese subjects after a high-fat meal were higher than those after a daily meal recommended by the EAS, indicating that specific cut-off points should be determined after a certain high-fat meal.

[Stored autologous blood transfusion does not increase recurrence of prostate cancer after radical prostatectomy: A preliminary study].

OBJECTIVE: To analyze the association of stored autologous blood transfusion (SABT) with tumor recurrence in PCa patients after radical prostatectomy and explore the application of SABT in this surgical procedure. METHODS: Forty-five PCa patients underwent radical prostatectomy in our hospital in recent five years, of whom, 20 received SABT (group A) and the other 25 allogeneic blood transfusion (group B) intraoperatively. After surgery, we followed up the patients regularly for 3－66 months by examination of the levels of total PSA (tPSA) and free PSA (fPSA), digital rectal examination (DRE), and MRI to observe the biochemical recurrence of the tumor. We compared the data obtained between the two groups of patients. RESULTS: In group A, 8 cases were in stages T1a－T1b and 12 in stages T2a－T2c, and in group B, 14 cases were in stages T1a－T1b and 11 in stages T2a－T2c. The volume of transfused blood was 800 ml in group A and 400－1 200 ml in group B. No statistically significant differences were observed between the two groups in the operation time, intraoperative blood loss or postoperative Gleason scores (P > 0.05), nor in the tPSA level or the results of DRE and MRI at 12, 24, 36, 48 and over 48 months (P > 0.05). CONCLUSIONS: SABT is safe for PCa patients undergoing radical prostatectomy and does not increase the tumor recurrence rate after surgery.

Correlation Between Apolipoprotein M and Inflammatory Factors in Obese Patients.

BACKGROUND The aim of this study was to observe apolipoprotein M (ApoM) level in obese patients and to explore its correlation with inflammatory factors. MATERIAL AND METHODS A total number of 96 participants were recruited and divided into 2 groups: the control group (or healthy group) whose participants had normal body weight (n=58), and the obese group with all its participants diagnosed with obesity (n=38). Data on blood pressure, body weight, height, body mass index, diastolic function of brachial artery endothelium, fasting venous blood glucose, blood lipids, plasmatic ApoM, interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), fasting insulin, and adiponectin levels were collected for both groups. RESULTS In the obese group, the levels of plasmatic ApoM, high-density lipoprotein cholesterol (HDL-C), and plasmatic adiponectin were significantly (p<0.05) decreased compared to the control group, and the levels of IL-6, TNF-α, CRP, and fasting insulin were significantly increased (p<0.05) compared to the control group. For the obese group, plasmatic ApoM level was positively correlated with HDL-C level and negatively correlated with levels of IL-6, TNF-α, CRP, insulin, and insulin resistance index. However, no significant correlations were revealed between plasmatic ApoM and the diastolic function of brachial artery endothelium, adiponectin level, blood pressure, and blood glucose level. CONCLUSIONS Obese patients showed significantly lower plasmatic ApoM levels than people with normal body weight, and ApoM level showed a strong correlation with CRP, TNF-α, and IL-6 levels, which indicated that ApoM might be regulated by these inflammatory factors.

Baseline levels of serum high sensitivity C reactive protein and lipids in predicting the residual risk of cardiovascular events in Chinese population with stable coronary artery disease: a prospective cohort study.

BACKGROUND: The contributions of inflammation, triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) to the residual risk of cardiovascular events have not been determined in a large cohort of Chinese population before. This study was aimed to investigate the association of serum levels of high sensitive C reactive protein (hs-CRP), TG and HDL-C with the residual risk of cardiovascular events in patients with stable coronary artery disease (CAD). METHODS: We enrolled 4090 patients with stable CAD from 13 hospitals in China. All participants received optimal medical treatment (OMT) for stable CAD suggested by guidelines and were followed. The endpoint measures were the first occurrence of a major adverse cardiovascular event (MACE), defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or unplanned coronary revascularization. Cox proportional regression analysis was conducted to identify independent predictors of MACE. RESULTS: We found that hs-CRP and HDL-C levels were associated with coronary lesion severity at baseline (both p < 0.001). After 3 months OMT, 91.2% (3730/4090) patients achieved the therapeutic goal for low density lipoprotein cholesterol (LDL-C) (< 1.8 mmoL/L). During a mean follow-up period of 39.5 months, 11.5% (471/4090) patients suffered MACE. In multivariate Cox proportional regression analysis, the hazard ratio for MACE was 1.17 (95% confidence interval: 1.07-1.28, p < 0.001) per standardized deviation in the log-transformed hs-CRP levels after adjustment for other traditional cardiovascular risk factors. However, baseline TG and HDL-C levels were not associated with MACE in this study. CONCLUSIONS: Baseline hs-CRP level was an independent predictor of residual risk of cardiovascular events in Chinese population with stable CAD. However, TG and HDL-C levels were not associated with MACE.

Effects and mechanisms of apolipoprotein A-V on the regulation of lipid accumulation in cardiomyocytes.

BACKGROUND: Apolipoprotein (apo) A-V is a key regulator of triglyceride (TG) metabolism. We investigated effects of apoA-V on lipid metabolism in cardiomyocytes in this study. METHODS: We first examined whether apoA-V can be taken up by cardiomyocytes and whether low density lipoprotein receptor family members participate in this process. Next, triglyceride (TG) content and lipid droplet changes were detected at different concentrations of apoA-V in normal and lipid-accumulation cells in normal and obese animals. Finally, we tested the levels of fatty acids (FAs) taken up into cardiomyocytes and lipid secretion through [14C]-oleic acid. RESULTS: Our results show that heart tissue has apoA-V protein, and apoA-V is taken up by cardiomyocytes. When HL-1 cells were transfected with low density lipoprotein receptor (LDLR)-related protein 1(LRP1) siRNA, apoA-V intake decreased by 53% (P<0.05), while a 37% lipid accumulation in HL-1 cells remain unchanged. ApoA-V localized to the cytoplasm and was associated with lipid droplets in HL-1 cells. A 1200 and 1800 ng/mL apoA-V intervention decreased TG content by 28% and 45% in HL-1 cells, respectively and decreased TG content by 39% in mouse heart tissue (P<0.05). However, apoA-V had no effects on TG content in either normal HL-1 cells or mice. The levels of FAs taken up into cardiomyocytes decreased by 43% (P < 0.05), and the levels of TG and cholesterol ester secretion increased by 1.2-fold and 1.6-fold, respectively (P < 0.05). CONCLUSION: ApoA-V is a novel regulator of lipid metabolism in cardiomyocytes.

Prevalence and risk factors associated with hypertension in the Chinese Qiang population.

Our aim is to investigate the prevalence and risk factors associated with hypertension among the Chinese Qiang population. From September 2012 to March 2013, a cross-sectional study was conducted in urban and rural communities of the Qiang population using multistage cluster sampling. A total of 2676 people aged above 20 years were enrolled in the analysis. Standardized mercury sphygmomanometer was used to measure the blood pressure twice after a 10-minute seated rest, and the average blood pressure was obtained. The hypertension prevalence among the population aged above 20 years was 13.9%, and age-standardized prevalence was 12.3%. Male and female prevalence of hypertension, as well as the prevalence in urban and rural areas, all increased with age. There were no significant differences between males and females and between urban and rural residents. Among hypertensive patients, 44.2% were aware of their hypertension, 38.0% were undergoing antihypertensive treatment, but only 10.5% achieved blood pressure control. Multivariate logistic regression analysis showed that the risk factors of hypertension included age, low income, overweight and obesity, family history of hypertension. The prevalence of hypertension in Chinese Qiang adults is significantly lower than the national level. Awareness, treatment, and control rates of hypertension were low in the Qiang population. Thus, hypertension-related health knowledge should be more aggressively delivered to improve public awareness and the capacity of community health services should be strengthened.

[Apolipoprotein A5 gene polymorphisms affect triglyceride metabolism and atherosclerotic cardiovascular diseases].

Apolipoprotein A5 (Apo A5) is a novel member in apolipoprotein family, which is proven to be an important regulator in triglyceride metabolism, especially in adjusting the TG content in plasma. Apo A5 gene polymorphisms affect triglyceride metabolism and atherosclerotic cardiovascular diseases. The research focuses on -1131T>C, c.56C>G, and c.553G>T.

Indispensable role of lipoprotein bound-ApoE in adipogenesis and endocytosis induced by postprandial TRL.

Diet-associated obesity is coexisted with postprandial hypertriglyceridemia that indicates increased number of triglyceride-rich lipoproteins (TRL). This study aimed to investigate the effect of postprandial TRL-bound apolipoprotein E (ApoE) on adipogenesis and potential mechanisms. 3T3-L1 cells were cultured with (i) human TRL (h-TRL) with or without insulin, or (ii) TRL from wild type mice (WT-TRL) or ApoE knock-out mice (EKO-TRL) and insulin. The differentiating adipocytes were incubated with different kinds of TRL labeled by red fluorescence and confocal microscopy was performed. Receptor associated protein (RAP), heparin or both were added to inhibit low density lipoprotein receptor family receptors, heparan sulfate proteoglycan or both, respectively. With the aid of insulin, postprandial h-TRL or WT-TRL, instead of EKO-TRL, successfully induced adipogenesis. Confocal microscopy revealed red fluorescence in the differentiating adipocytes treated with h-TRL or WT-TRL, but not with EKO-TRL. RAP markedly reduced red fluorescence within the differentiating adipocytes, while heparin had little impact. The low density lipoprotein receptor related protein 1 protein showed upward trend with the increase of TRL concentrations. Taken together, lipoprotein-bound ApoE was required in both postprandial TRL-induced adipogenesis and TRL endocytosis by the differentiating adipocytes, the latter could be partially through low density lipoprotein receptor family dependent-pathway.

Folic Acid Therapy Reduces the First Stroke Risk Associated With Hypercholesterolemia Among Hypertensive Patients.

BACKGROUND AND PURPOSE: We sought to determine whether folic acid supplementation can independently reduce the risk of first stroke associated with elevated total cholesterol levels in a subanalysis using data from the CSPPT (China Stroke Primary Prevention Trial), a double-blind, randomized controlled trial. METHODS: A total of 20 702 hypertensive adults without a history of major cardiovascular disease were randomly assigned to a double-blind daily treatment of an enalapril 10-mg and a folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. The primary outcome was first stroke. RESULTS: The median treatment duration was 4.5 years. For participants not receiving folic acid treatment (enalapril-only group), high total cholesterol (≥200 mg/dL) was an independent predictor of first stroke when compared with low total cholesterol (<200 mg/dL; 4.0% versus 2.6%; hazard ratio, 1.52; 95% confidence interval, 1.18-1.97; P=0.001). Folic acid supplementation significantly reduced the risk of first stroke among participants with high total cholesterol (4.0% in the enalapril-only group versus 2.7% in the enalapril-folic acid group; hazard ratio, 0.69; 95% confidence interval, 0.56-0.84; P<0.001; number needed to treat, 78; 95% confidence interval, 52-158), independent of baseline folate levels and other important covariates. By contrast, among participants with low total cholesterol, the risk of stroke was 2.6% in the enalapril-only group versus 2.5% in the enalapril-folic acid group (hazard ratio, 1.00; 95% confidence interval, 0.75-1.30; P=0.982). The effect was greater among participants with elevated total cholesterol (P for interaction=0.024). CONCLUSIONS: Elevated total cholesterol levels may modify the benefits of folic acid therapy on first stroke. Folic acid supplementation reduced the risk of first stroke associated with elevated total cholesterol by 31% among hypertensive adults without a history of major cardiovascular diseases. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885.

Metformin ameliorates obesity-associated hypertriglyceridemia in mice partly through the apolipoprotein A5 pathway.

INTRODUCTION: Apolipoprotein A5 (apoA5) is a key regulator of triglyceride (TG) metabolism. This study is to investigate the role of apoA5 in obesity-associated hypertriglyceridemia and metformin-related hypotriglyceridemic actions. METHODS: Two obese mouse models, including high-fat diet-induced obese mice and ob/ob obese mice, were adopted. The effects of low- and high-dose metformin were determined on plasma and hepatic TG and apoA5 of these obese mice. Besides, the effects of metformin on TG and apoA5 were also detected in mouse and human hepatocytes in vitro. RESULTS: (1) Plasma apoA5 levels in the obese mice were markedly elevated and positively correlated with TG. Hepatic TG contents and apoA5 expressions were also remarkably increased in the obese mice. (2) Metformin dose-dependently decreased hepatic and plasma TG and apoA5 in the obese mice. Similarly, metformin dose-dependently reduced cellular TG contents and apoA5 expressions in hepatocytes in vitro. Compared to APOA5 knock-down (KD), metformin plus APOA5 KD resulted in more TG reduction of hepatocytes. CONCLUSION: Increased hepatic and plasma apoA5 could be a result of obesity-associated hypertriglyceridemia, and metformin displays hypotriglyceridemic effects on obese mice partly via the apoA5 pathway.

Prevalence, awareness, treatment, and control of hypertension among China's Sichuan Tibetan population: A cross-sectional study.

BACKGROUND: Our aim is to investigate the prevalence, awareness, treatment, and control status of hypertension and explore the associated factors among Sichuan Tibetan population. METHODS: A cross-sectional investigation was conducted in the Sichuan Tibetan region from to September 2013 to March to 2014. Three thousand two hundred and forty persons were included in the study through a multi-stage stratified clustering sampling. Participants received questionnaires and physical examination. Blood pressure (BP) was recorded three times after 5 min of rest with the mean taken as the final BP. Hypertension was defined according the 2010 Chinese guidelines for the management of hypertension. RESULTS: Prevalence of hypertension was 45.7%. The proportion of different stages (1-3) of hypertension was 31.7%, 9.2%, and 7.6% for males and 26.3%, 9.5%, and 6.0% for females. The rate of awareness, treatment, and control of hypertension were 4.9%, 21.3%, and 3.0% for males and 7.5%, 24.5%, and 3.1% for females. Multiple-factor analysis found that age, overweight or obesity (odds ratio(OR)=1.16), drinking alcohol (OR = 1.29, 95% confidence interval (CI):1.07-1.54), increased waist circumference (OR = 1.81, 95%CI: 1.39-2.36), family history of hypertension (OR = 1.51, 95%CI; 1.28-1.78), higher salt intakes (OR = 1.62, 95%CI: 1.24-2.11), long duration of sleep (OR = 1.05, 95%CI: 1.01-1.09), rural area (OR = 1.99, 95%CI: 1.64-2.41), and drinking coffee at times (OR = 0.71, 95%CI:0.57-0.87) were related to hypertension. CONCLUSION: Prevalence of hypertension in Sichuan Tibetan was significantly higher than the national level with low rates of awareness, treatment, and control of hypertension. Intervention measurements are needed to change some unhealthy lifestyles, behaviors, and habits in this region.

Long-term atorvastatin-ezetimibe-probucol triple therapy for homozygous familial hypercholesterolaemia from early childhood.

In this observational case report, we share our experience of achieving >40% LDL cholesterol reduction in four Chinese homozygous familial hypercholesterolaemia children below 8 years of age with a triple combination of atorvastatin, probucol, and ezetimibe for >6 years. Within a follow-up duration of 6-13 years, this triple therapy achieved significant reduction of LDL cholesterol as well as an impressive regression of xanthomas in all paediatric cases. All the children remained free from treatment-related adverse responses and cardiovascular events throughout follow-up.

Myocyte Enhancer Factor 2A Regulates Hydrogen Peroxide-Induced Senescence of Vascular Smooth Muscle Cells Via microRNA-143.

Myocyte enhancer factor 2A (MEF2A) is involved in vascular smooth muscle cell (VSMC) proliferation, migration, and senescence. MicroRNA-143/145 (miR-143/145), which may be regulated by MEF2A, is known to promote cellular senescence. We hypothesized that MEF2A may promote VSMC senescence via miR-143/145. VSMC senescence was induced by hydrogen peroxide (H(2)O(2)), followed by detection using a senescence-associated ß-galactosidase staining kit. The MEF2A protein, mRNA, and miR-143/145 levels in VSMCs were detected using Western blot analysis and SYBR green real-time quantitative PCR, respectively. We further manipulated the expression levels of MEF2A and miR-143 through viral or transient transfection. VSMC proliferation and migration were determined by methylthiazolyldiphenyl-tetrazolium bromide and Millicell chamber, respectively. Both MEF2A and miR-143, but not miRNA-145, were up-regulated in senescent VSMCs. Overexpression of either MEF2A or miR-143 significantly enhanced VSMC senescence, but reduced proliferation and migration. MEF2A knockdown or miR-143 inhibitor suppressed cellular senescence and increased proliferation and migration. We further revealed AKT signaling as a potential miR-143 target, and an induction of miR-143 expression by MEF2A via KLF2. Additionally, overexpression of MEF2A and miR-143 resulted in synergistic effects on promotion of senescence, and MEF2A knockdown and miR-143 reduction by inhibitor had synergistic inhibitory effects. Finally, MEF2A barely promoted VSMC senescence when miR-143 was inhibited, and miR-143 overexpression antagonized the inhibitory effect of MEF2A knockdown on VSMC senescence. Our results revealed a link and interaction between MEF2A and miR-143 and suggested a potential mechanism for MEF2A to regulate H(2)O(2) -induced VSMC senescence.

Exosome and its roles in cardiovascular diseases.

Exosomes are nanosized vesicles secreted by cells, which are capable of carrying signaling molecules in the forms of protein, mRNA and miRNA to serve as the platforms for complex intercellular communications. During the past few years, increasing efforts have been devoted to exosome research, and tremendous progress has been made in terms of identifying the molecular composition, elucidating the mechanisms and regulations of biogenesis and characterizing the functions in a variety of physiological and pathological settings including cardiovascular diseases, a leading cause of morbidity and mortality in modern society. This review provides an update on exosome research and summarizes the roles of exosomes in cardiovascular diseases.

The Tripartite Model for Assessing Symptoms of Depression and Anxiety: Psychometric Properties of the Chinese Version of the Mood and Anxiety Symptoms Questionnaire in Patients With Essential Hypertension.

BACKGROUND: In patients with hypertension, psychosocial factors, such as depressive symptoms and anxiety, are associated with reduced quality of life and triple the risk of nonadherence with medical treatment regimens. Thus, screening tests are crucial to identify patients who may require further assessment and treatment. OBJECTIVES: The objective of the current study was to test the psychometric properties of the Chinese version of the Mood and Anxiety Symptoms Questionnaire-Short Form (MASQ-SF-C) in patients with essential hypertension. METHODS: The MASQ-SF-C, the Center for Epidemiologic Studies Depression Scale (CES-D), and the State-Trait Anxiety Inventory (STAI) were administered to a convenience sample of 869 hypertensive patients in 4 hospitals. A confirmatory factor analysis was used to test the tripartite model. We evaluate the internal consistency of the MASQ-SF-C and we used the Bland-Altman approach to evaluate convergent validity between the MASQ-SF-C t score and symptoms of (1) depressive symptoms and (2) anxiety. RESULTS: Cronbach's α coefficient for the total MASQ-SF-C was .95, and Cronbach's α coefficients for the 3 subscales were .83 for anhedonic depression (AD), .91 for anxiety arousal (AA), and .94 for general distress (GD), indicating adequate internal consistency reliability. The mean interitem correlation coefficients were as follows: MASQ-SF-C, 0.29; AD, 0.28; AA, 0.38; and GD, 0.40. The 1-month test-retest reliability for the MASQ-SF-C was 0.72. Confirmatory factor analyses indicated that the 3 first-order factors (GD, AD, and AA) fit the data well (nonnormed fit index = 0.953, comparative fit index = 0.936, incremental fit index = 0.936, root-mean-square error of approximation = 0.038). CONCLUSIONS: This study supported the reliability and validity of the MASQ-SF-C, indicating that it can be used for assessing depressive symptoms and anxiety concurrently in Chinese-speaking patients with hypertension.