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This study aimed to investigate the prevalence of dyslipidemia and its related factors among urban adults aged 35 to 79 years in Southwestern China. From September 2013 to March 2014, a multi-stage sampling was conducted, and a total of 10,221 people aged 35–79 years living in Chengdu and Chongqing were included. More than 30 investigators were trained in data collection, including questionnaire, anthropometric measurements and blood biomarkers testing. The prevalence of high triglycerides (≥ 2.3 mmol/L), high total cholesterol (≥ 6.2 mmol/L), high low-density lipoprotein cholesterol (≥ 4.1 mmol/L), low high-density lipoprotein cholesterol (

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.

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.

This study aimed to investigate the prevalence of dyslipidemia and its related factors among adults aged 35 to 79 years in southwest China. From September 2013 to March 2014, a multi-stage, stratified sampling was conducted on 10221 people aged 35–79 years living in Chengdu and Chongqing by using the method of field questionnaire survey and measurement. The prevalence of high triglycerides (≥ 2.3 mmol/L), high total cholesterol (≥ 6.2 mmol/L), high low-density lipoprotein cholesterol (≥ 4.1 mmol/L), low high-density lipoprotein cholesterol (

CA extern - Weitere Nicht-UDE-Autoren sind nicht genannt. Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007. © 2020 Hellenic Society of Cardiology

Background: Xuezhikang, an extract of red yeast rice, effectively lowers fasting and postprandial triglyceride (TG) levels. It was unknown that whether Xuezhikang could contribute the lipid management goals, low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (nonHDL-C) at fasting and postprandial states in patients with coronary artery disease (CAD).Methods: Fifty CAD patients were divided into Xuezhikang (XZK, n=25) group and control (CON, n=25) group randomly to receive red yeast rice exact, 1200mg/d Xuezhikang capsules or not for 6 weeks (6w). Blood lipids were detected repeatedly before and after 6w at 0, 2, 4 and 6 hours (h) after a standard breakfast with 800kcal.Result: When taking all patients as a whole (n=50), serum LDL-C level decreased while TG and RC levels increased significantly at 2, 4 and 6 h after breakfast (P＜0.05). Serum nonHDL-C level mildly but significantly increased at 4h and 6h after breakfast (P＜0.05). Short-term Xuezhikang treatment decreased tAUCs of TC, TG, LDL-C, nonHDL-C and RC whereas increased that of HDL-C significantly (P＜0.05). Serum LDL-C level showed a drop of 27.8%, 28.1%, 26.2%, 25.3% at 0, 2, 4 and 6 h, respectively, after breakfast. Serum nonHDL-C level showed a drop of 27.6%, 28.7%, 29.0% and 28.0% at 0, 2, 4 and 6 h, respectively. There was no significant difference in the percentages of reduction in LDL-C or nonHDL-C level among four time-points.Conclusions: Xuezhikang significantly decreased LDL-C or nonHDL-C level with similar percentages of reduction between fasting and postprandial states in patients with CAD, indicating that postprandial blood lipids detected at the same time point after a daily meal could replace fasting blood lipids to evaluate the efficacy of cholesterol-lowering therapy in CAD patients, unwilling or unable to keep a fasting state.

In this paper, we sought to explore the relationship between apolipoprotein AV (APOAV) overexpression and insulin resistance in hepatocytes. The insulin-resistant HepG2 cell model was constructed, and then,APOAV-overexpressed HepG2 cells (B-M) were induced by infecting with a recombinant adenovirus vector. Microarray data were developed from B-M samples compared with negative controls (A-con), and the microarray data were analyzed by bioinformatic methods.APOAV-overexpression induced 313 upregulated genes and 563 downregulated ones in B-M sample. The differentially expressed genes (DEGs) were significantly classified in fat digestion and absorption pathway. Protein-protein interaction network was constructed, andAGTR1(angiotensin II receptor type 1) andP2RY2(purinergic receptor P2Y, G-protein coupled 2) were found to be the significant nodes closely related with G-protein related signaling. Additionally, overexpression ofAPOAVcould change the expression of Glut4 and release the insulin resistance of hepatic cells. Thus,APOAVoverexpression may prevent the insulin resistance in liver cells by mediating the genes such asAGTR1andP2RY2.

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.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.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 (P0.05), nor in the tPSA level or the results of DRE and MRI at 12, 24, 36, 48 and over 48 months (P0.05).SABT is safe for PCa patients undergoing radical prostatectomy and does not increase the tumor recurrence rate after surgery.

Backgroud: We investigated the lipid-lowering efficacy and safety of coenzyme A (CoA) versus fenofibrate in Chinese patients with moderate dyslipidemia. Methods: A total of 417 subjects (aged 18���75 years) diagnosed with moderate dyslipidemia (triglyceride, 2.3-6.5 mmol/L) from 13 large cardiovascular centers in China were recruited and randomly divided into a fenofibrate group (n = 207), which received 200mg of fenofibrate orally once daily, and a CoA group (n = 210), which received 400mg of CoA orally once a day. Blood lipoproteins, liver and renal function, creatine kinase, and blood glucose were measured at baseline and after 4 and 8 weeks of treatment. Results: The baseline triglyceride (TG) level in the fenofibrate group and the CoA group was 3.39 �� 0.99 mmol/L and 3.60 �� 1.11 mmol/L, respectively. After treatment for 4 and 8 weeks with fenofibrate, TG was reduced by 31.62% and 33.13%. In the CoA group, TG was reduced by 17.29% and 23.80%. Compared with baseline, total cholesterol (TC) was significantly decreased in both groups after either 4 or 8 weeks of treatment (P Conclusions: Compared with fenofibrate, CoA has less effect on reducing plasma TG levels in subjects with moderate dyslipidemia. However, it has fewer adverse effects.

Background: Oxidized low-density lipoprotein (ox-LDL)-induced oxidative stress and endothelial apoptosis are essential for atherosclerosis. Our previous study has shown that ox-LDL-induced apoptosis is mediated by the protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2α-subunit (eIF2α)/CCAAT/enhancer-binding protein homologous protein (CHOP) endoplasmic reticulum (ER) stress pathway in endothelial cells. Statins are cholesterol-lowering drugs that exert pleiotropic effects including suppression of oxidative stress. This study aimed to explore the roles of simvastatin on ox-LDL-induced ER stress and apoptosis in endothelial cells. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with simvastatin (0.1, 0.5, or 2.5 µmol/L) or DEVD-CHO (selective inhibitor of caspase-3, 100 µmol/L) for 1 h before the addition of ox-LDL (100 µg/ml) and then incubated for 24 h, and untreated cells were used as a control group. Apoptosis, expression of PERK, phosphorylation of eIF2α, CHOP mRNA level, and caspase-3 activity were measured. Comparisons among multiple groups were performed with one-way analysis of variance (ANOVA) followed by post hoc pairwise comparisons using Tukey’s tests. A value of P < 0.05 was considered statistically significant. Results: Exposure of HUVECs to ox-LDL resulted in a significant increase in apoptosis (31.9% vs. 4.9%, P < 0.05). Simvastatin (0.1, 0.5, and 2.5 µmol/L) led to a suppression of ox-LDL-induced apoptosis (28.0%, 24.7%, and 13.8%, F = 15.039, all P < 0.05, compared with control group). Ox-LDL significantly increased the expression of PERK (499.5%, P < 0.05) and phosphorylation of eIF2α (451.6%, P < 0.05), if both of which in the control groups were considered as 100%. Simvastatin treatment (0.1, 0.5, and 2.5 µmol/L) blunted ox-LDL-induced expression of PERK (407.8%, 339.1%, and 187.5%, F = 10.121, all P < 0.05, compared with control group) and phosphorylation of eIF2α (407.8%, 339.1%, 187.5%, F = 11.430, all P < 0.05, compared with control group). In contrast, DEVD-CHO treatment had no significant effect on ox-LDL-induced expression of PERK (486.4%) and phosphorylation of eIF2α (418.8%). Exposure of HUVECs to ox-LDL also markedly induced caspase-3 activity together with increased CHOP mRNA level; these effects were inhibited by simvastatin treatment. Conclusions: This study suggested that simvastatin could inhibit ox-LDL-induced ER stress and apoptosis in vascular endothelial cells. Key words: Apoptosis; Endoplasmic Reticulum Stress; Endothelial Cells; Oxidized Low-Density Lipoprotein; Simvastatin

It has previously been demonstrated that apolipoprotein A5 (apoA5) can be internalized by human adipocytes and significantly decreases intracellular triglyceride content. In the present study, endocytosis of apoA5 by adipocytes under different conditions, and the underlying mechanism by which apoA5 regulates cellular triglyceride storage, was investigated. The results revealed that the apoA5 protein was detected in human subcutaneous abdominal adipose tissues. In addition, the uptake of apoA5 was attenuated in human obese adipose tissues and in cultured adipocytes with hypertrophy or insulin resistance. Low-density lipoprotein receptor protein 1 (LRP1) knockdown in adipocytes resulted in a decrease in internalized apoA5 content, suggesting that LRP1 serves a role in apoA5 uptake. Treatment of adipocytes with apoA5 decreased the expression of the lipid droplet-associated proteins such as cidec and perilipin. ApoA5-treated adipocytes demonstrated an increase in lipolysis activity and expression of uncoupling protein 1, which is the molecular effector of thermogenesis in brown adipocytes. These results suggested that decreased triglyceride accumulation in adipocytes induced by apoA5 may be associated with enhanced lipolysis and energy expenditure, which may result from reduced expression of cidec and perilipin. In conclusion, the present study demonstrated a novel role of apoA5 in regulating the intracellular triglyceride metabolism of adipocytes. The results of the present study suggested that apoA5 may serve as a potential therapeutic target for the treatment of obesity and its related disorders.

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

Since the withdrawal of cerivastatin, statin-fibrate combination therapy has been questioned in China due to safety concern. The objective of this study was to evaluate the efficacy and safety profile of fenofibrate as an add-on in patients with dyslipidemia despite receiving statin therapy.This was a prospective, multi-center, single-arm, open-label study conducted in Chinese dyslipidemia patients with high CV risk. Fenofibrate (200mg daily) was added to the existing statin treatment for 8weeks. Lipid profile and safety parameters were measured and compared between baseline and after the treatment. Five hundred and six subjects were enrolled from 28 sites from 14 cities nationwide across China.After 8weeks of fenofibrate treatment, the mean blood triglyceride level decreased to 1.77mmol/L (38.1% reduction vs. 3.00mmol/L at the baseline; p0.01). Mean high-density lipoprotein cholesterol (high density lipoprotein cholesterol) was increased to 1.22mmol/L (by 17.4% from 1.07mmol/L at the baseline; p0.01). No case of severe muscle damage (defined as elevated creatine kinase over 5 times of upper limit of normal (ULN) or rhabdomyolysis was observed.In statin-treated patients with high CV risk who had elevated triglyceride, adding fenofibrate could improve lipid profile with acceptable safety profiles.

Background: Adipocytes behave like a rich source of pro-inflammatory cytokines including monocyte chemoattractant protein-1 (MCP-1). Oxidized low-density lipoprotein (oxLDL) participates in the local chronic inflammatory response, and high-density lipoprotein could counterbalance the proinflammatory function of oxLDL, but the underlying mechanism is not completely understood. This study aimed to evaluate the effect of apolipoprotein A-I mimetic peptide L-4F on the secretion and expression of MCP-1 in fully differentiated 3T3-L1 adipocytes induced by oxLDL and to elucidate the possible mechanisms. Methods: Fully differentiated 3T3-L1 adipocytes were incubated in the medium containing various concentration of L-4F (0–50 μg/ml) with oxLDL (50 μg/ml) stimulated, with/without protein kinase A (PKA) inhibitor H-89 (10 μmol/L) preincubated. The concentrations of MCP-1 in the supernatant, the mRNA expression of MCP-1, the levels of CCAAT/enhancer binding protein α (C/EBPα), and CCAAT/enhancer binding protein β (C/EBPβ) were evaluated. The monocyte chemotaxis assay was performed by micropore filter method using a modified Boyden chamber. Results: OxLDL stimulation induced a significant increase of MCP-1 expression and secretion in 3T3-L1 adipocytes, which were inhibited by L-4F preincubation in a dose-dependent manner. PKA inhibitor H-89 markedly reduced the oxLDL-induced MCP-1 expression, but no further decrease was observed when H-89 was used in combination with L-4F (50 μg/ml) ( P > 0.05). OxLDL stimulation showed no significant effect on C/EBPα protein level but increased C/EBPβ protein level in a time-dependent manner. H-89 and L-4F both attenuated C/EBPβ protein level in oxLDL-induced 3T3-L1 adipocytes. Conclusions: OxLDL induces C/EBPβ protein synthesis in a time-dependent manner and enhances MCP-1 secretion and expression in 3T3-L1 adipocytes. L-4F dose-dependently counterbalances the pro-inflammatory effect of oxLDL, and cyclic AMP/PKA-C/EBPβ signaling pathway may participate in it.

Fluid flow tests on a series of one-inlet-two-outlet specimens with fracture intersections are conducted under conditions of high hydraulic gradient ( J = 100–101 ) and high Reynolds number (Re = 10 4–105). The fluid flow through the intersections is recorded using a single lens reflex (SLR) camera. It was demonstrated that the intersection shapes can enhance the strong nonlinearity of the fluid flow at high J and high Re. The angle pattern, which is represented by the case of intersecting fractures, affects the ratio of the outlet flow rate distribution (e). The detailed effects for all cases can be categorized into three models via quantitative analysis. The intersection shapes of model I angle patterns result in larger e. However, the intersection shapes of model II and model III angle patterns result in smaller e compared. In addition, the distribution fitting curve of the peak e values is provided. A modified Gaussian distribution function is formulated to fit the experimental curves. Furthermore, the relationship between e and the angle patterns is elaborated.

Recent studies have suggested that lipoprotein(a) [Lp(a)] is associated with cardiovascular disease (CVD). However, the contribution of Lp(a) to residual risk of CVD has not been determined in Chinese populations. We conducted a prospective study to evaluate the association between Lp(a) and the risk of major adverse cardiovascular events (MACEs) in patients with stable coronary artery disease (CAD) who received optimal medication treatment (OMT). The study enrolled 1602 patients with stable CAD from 5 hospitals in China. The baseline clinical characteristics and follow-up MACE data for the patients were recorded. Coronary lesion severity was assessed by the Gensini scoring system. All-cause death, non-fatal myocardial infarction, non-fatal stroke and unplanned coronary revascularization were considered MACEs. We found that plasma Lp(a) levels were positively associated with coronary lesion severity at baseline (p

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

Aims Ionic perturbation in vascular smooth muscle cells contributes to cerebrovascular remodelling in the setting of hypertension, but the role of transient receptor potential (TRP) channel superfamily remains unknown. The present study was conducted to define the contribution of TRP channels to cerebrovascular remodelling. Methods and results By integrating quantitative PCR, western blotting, patch clamping, and Ca2+ imaging, we identified TRP channel, subfamily canonical, member 3 (TRPC3) as the channel subtype most considerably elevated in basilar arteries of two-kidney, two-clip stroke-prone hypertensive rats. Importantly, administration of pyrazole 3 (Pyr3), a TRPC3 channel blocker, attenuated cerebrovascular remodelling. During hypertension, epidermal growth factor receptor (EGFR) was transactivated, as evidenced by marked EGFR phosphorylation, increased pro-HB-EGF shedding, and elevated activity of ADAM17 (HB-EGF sheddase). ADAM17 activity was increased owing to enhanced activation rather than elevated expression. Remarkably, Pyr3 treatment suppressed EGFR transactivation in hypertension. In proliferating basilar artery smooth muscle cells or basilar arteries of hypertensive rats, co-immunoprecipitation assay revealed an interaction between TRPC3 and ADAM17 upon Ang II stimulation. Conclusion Collectively, we demonstrated that enhanced EGFR transactivation, due to increased TRPC3 expression and functional coupling of TRPC3/ADAM17, resulted in cerebrovascular remodelling. Therefore, TRPC3-induced EGFR transactivation may be therapeutically exploited to prevent hypertension-induced cerebrovascular remodelling.

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 β-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.

Familial hypercholesterolaemia (FH) is an autosomal dominant genetic disorder, associated with elevated level of serum low-density lipoprotein-cholesterol (LDL-C), which can lead to premature cardiovascular disease (CVD). Mutations in low density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) have been identified to be the underlying cause of this disease. Genetic research of FH has already been extensively studied all over the world. However, reports of FH mutations in the Chinese population are still limited. In this paper, 20 unrelated FH families were enrolled to detect the candidate gene variants in Chinese FH population by DNA direct sequencing. We identified 12 LDLR variants in 13 FH probands. Importantly, we first reported two unique mutations (c.2000_2000 delG/p.C667LfsX6 and c.605T>C/p.F202S) in LDLR gene. Our discoveries expand the spectrum of LDLR mutations and contribute to the genetic diagnosis and counseling for FH patients.

Aim: Previous studies have demonstrated that the dysregulated-secretion of adipokines by adipocytes may contribute to obesity-associated atherosclerosis (As) and high density lipoprotein (HDL) may protect against atherogenesis through multiple pathways. This study was to explore the effect of HDL on the oxLDL uptake in inflammatory adipocytes stimulated by endotoxin lipopolysaccharide (LPS) and the possible mechanism. Methods and Results: 3T3-L1 adipocytes were cultured and induced to differentiation and maturation. Acute inflammation in adipocytes was induced by LPS (100 ng/ml) for 6 hours. The adipocytes were pretreated with HDL in various concentrations (10, 50, 100 μg/ml) for 16 hours or with specific PPARγ antagonist (GW9662, 10 μM) or agonist (Rosiglitazone, 10 μM) for 30 min before administration of LPS. The results showed that LPS significantly increased the release of inflammation-related adipokines, such as monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor 1 (PAI-1), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-8 and IL-6, while decreasing the release of leptin and adiponectin. Meanwhile, LPS reduced the uptake and degradation of 125 I-oxLDL, and down-regulated the expression of PPARγ and CD36. Pretreatment with HDL dose-dependently affected the release of IL-8 and IL-6 and the reduced uptake and degradation of oxLDL of adipocytes stimulated by LPS, accompanied with marked upregulation of PPARγ and CD36 expression. Pretreatment with GW9662 markedly inhibited the upregulation of CD36 expression mediated by HDL (100 μg/ml), while the effects of Rosiglitazone were opposite to GW9662. Conclusions: HDL may increase oxLDL uptake of inflammatory adipocytes stimulated by LPS via upregulation of PPARγ/CD36 pathway, which may be a new mechanism of anti-atherosclerosis mediated by HDL.

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.

Objective This study aimed to investigate the effect of physicians’ characteristics and knowledge of LDL–C target goals on the quality of lipid management in China. Methods A total of 25 317 dyslipidemia patients who had taken lipid–lowering medication for >3 months were enrolled in our study. Patients’ demographic data, medical history, lipid profile, their physician’s specialty and professional title and their hospital level as well as their LDL–C goal opinions were recorded. Results Questionnaires were completed by 926 physicians with 6 different specialties and 4 professional statuses, in 3 different–level hospitals. Most (74.5%) of the physicians recognized the importance of considering LDL–C serum concentration for treating dyslipidemia, and set target LDL–C goals according to the 2007 Chinese guidelines for 83.4% of their patients. The LDL–C goal achievement rate was significantly higher for patients whose physicians’ knowledge of LDL–C target goals was consistent with guideline recommendations, compared with those whose physicians’ knowledge was inconsistent with the guidelines (60.4% vs 31.1%, P

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.

Statins are widely used to reduce cardiovascular risk. Unfortunately, some patients still experience cardiovascular events though prescribed with high-intensity statins. Metformin, an anti-diabetic drug, was reported to possess anti-atherosclerotic effects. Therefore, the experiments were designed to evaluate whether combined use of metformin and atorvastatin can achieve additional benefits. In rabbits fed a high-cholesterol diet, we evaluated the effects of the combination therapy on atherosclerotic plaques, lipid profiles, blood glucose levels, liver and kidney functions. Effects of combination therapy on cholesterol efflux and the expression of related transporters were studied in vitro. Our results showed that the combination therapy induced a more significant decrease in atherosclerotic lesion area than atorvastatin without additional lipid-lowering effect. The combination therapy significantly increased the percentage of large high-density lipoprotein subfraction. The intravenous glucose tolerance test showed that atorvastatin-treated rabbits had an increased area under the curve for time-dependent glucose levels after a bolus injection of glucose, which was completely reversed by metformin treatment. In cultured macrophages, co-treatment with metformin and atorvastatin promoted cholesterol efflux and up-regulated expression of ATP-binding cassette transporters A1 and G1. Taken together, our results suggest that atorvastatin/metformin combination therapy may achieve additional anti-atherosclerotic benefits likely through increasing cholesterol efflux in macrophages.

Exchangeable apolipoproteins play an important role in systemic lipid metabolism, especially for lipoproteins with which they are associated. Recently, emerging evidence has suggested that exchangeable apolipoproteins, such as apolipoprotein A4 (apoA4), apolipoprotein A5 (apoA5), apolipoprotein C3 (apoC3) and apolipoprotein E (apoE), also exert important effects on intracellular lipid homeostasis. There is a close link between lipid metabolism in adipose tissue and liver because the latter behaves as the metabolic sensor of dysfunctional adipose tissue and is a main target of lipotoxicity. Given that the energy balance between these two major lipogenic organs is intimately involved in the pathogenesis of obesity and non-alcoholic fatty liver disease (NAFLD), we here review recent findings concerning the intracellular function of exchangeable apolipoproteins in triglyceride metabolism in adipocytes and hepatocytes. These apolipoproteins may act as mediators of crosstalk between adipose tissue and liver, thus influencing development of obesity and hepatosteatosis. This review provides new insights into the physiological role of exchangeable apolipoproteins and identifies latent targets for therapeutic intervention of obesity and its related disorders.

A novel synthetic dual-domain apolipoprotein (apo)-mimetic peptide, Ac-hE-18A-NH2, has been proposed to possess several apo A-I- and apo E-mimetic properties. This study investigated the protective effect of this peptide on oxidized low-density lipoprotein (ox-LDL)-induced apoptosis in RAW264.7 cells. For this purpose, RAW264.7 cells were exposed to 50 µg/ml ox-LDL for 48 h, and then incubated with the peptide Ac-hE-18A-NH2 at various concentrations. Apoptosis was detected using annexin V-fluorescein isothiocyanate staining and flow cytometric analysis. The study revealed that the peptide Ac-hE-18A-NH2 (1, 10 and 50 µg/ml) inhibited ox-LDL-mediated apoptosis, and this was accompanied by an increased rate of intracellular cholesterol efflux, and decreased total cholesterol levels in the cells in a concentration-dependent manner. The peptide also decreased caspase-3 activity and increased B-cell lymphoma 2 protein (Bcl-2) expression in macrophages in a dose-dependent manner. Moreover, blockage of cholesterol efflux by brefeldin A decreased the protective effect of Ac-hE-18A-NH2 against ox-LDL induced apoptosis, while increasing the cholesterol efflux by β-cyclodextrin administration led to a marked decrease in the rate of apoptosis of the cells. These findings demonstrate that the apo-mimetic peptide Ac-hE-18A-NH2 exerts a protective effect against apoptosis by reducing the accumulation of cholesterol.

Background Familial hypercholesterolemia (FH) is the first molecularly and clinically characterized genetic disease of lipid metabolism. It is an autosomal dominant disorder with significantly elevated levels of total cholesterol and low density of lipoprotein cholesterol in serum, which would lead to extensive xanthomas and premature coronary heart disease. Mutations in low density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 and Apo lipoprotein B-100 (APOB) have been identified to be the underlying cause of this disease. Methods Genetic testing and reports of the mutations in the Chinese population are still limited. In this study, 11 unrelated Chinese FH families were enrolled to detect the candidate gene variants by DNA direct sequencing. Results and conclusion We identified 12 mutations (11 in LDLR and one in APOB) in ten FH families. Three novel LDLR mutations (c.516C>A/p.D172E, c.1720C>A/p.R574S and c.760C>T/p.Q254X) were identified and co-segregated with the affected individuals in the families. Our discoveries not only further supports the significant role of LDLR in FH, but also expands the spectrum of LDLR mutations. These new insights will contribute to the genetic diagnosis and counseling of FH patients.

Statins are effective cholesterol-lowering drugs for reducing the risks of mortality and morbidity of cardiovascular diseases. Increasing evidence has shown that statin use is associated with a significant beneficial effect in patients with ischemic stroke. Both pre-stroke and post-stroke statin use has been found to be beneficial in ischemic stroke. Furthermore, good adherence is associated with a better clinical outcome, and statin withdrawal is associated with a poor functional outcome in patients with ischemic stroke. High-intensity statin therapy is advocated for the treatment of ischemic stroke. However, there are concerns regarding the adverse effects associated with statin use in ischemic stroke such as intracranial hemorrhage. In this review, we summarize the beneficial effect of statin use in ischemic stroke and discuss the potential risks associated with statin therapy.

Cigarette smoking has been identified as an independent and preventable risk factor for atherosclerosis and cardiovascular disease. Population studies have shown that plasma high density lipoprotein (HDL) cholesterol levels are inversely related to the risk of developing cardiovascular disease. Cigarette smoking is associated with reduced HDL cholesterol levels. Cigarette smoking can alter the critical enzymes of lipid transport, lowering lecithin: cholesterol acyltransferase (LCAT) activity and altering cholesterol ester transfer protein (CETP) and hepatic lipase activity, which attributes to its impact on HDL metabolism and HDL subfractions distribution. In addition, HDL is susceptible to oxidative modifications by cigarette smoking, which makes HDL become dysfunctional and lose its atheroprotective properties in smokers. Therefore, cigarette smoking has a negative impact on both HDL quantity and function, which can explain, in part, the increased risk of cardiovascular disease in smokers.

Background Epoxyeicosatrienoic acids (EETs) are natural angiogenic mediators regulated by soluble epoxide hydrolase (sEH). Inhibitors of sEH can stabilize EETs levels and were reported to reduce atherosclerosis and inhibit myocardial infarction in animal models. In this work, we investigated whether increasing EETs with the sEH inhibitor t -AUCB would increase angiogenesis related function in endothelial progenitor cells (EPCs) from patients with acute myocardial infarction (AMI). Methods and results EPCs were isolated from 50 AMI patients and 50 healthy subjects (control). EPCs were treated with different concentrations of t -AUCB for 24h with or without peroxisome proliferator activated receptor γ (PPARγ) inhibitor GW9662. Migration of EPCs was assayed in trans-well chambers. Angiogenesis assays were performed using a Matrigel-Matrix in vitro model. The expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α) mRNA and protein in EPCs was measured by real-time PCR or Western blot, respectively. Also, the concentration of EETs in the culture supernatant was detected by ELISA. The activity of EPCs in the AMI patient group was reduced compared to healthy controls. Whereas increasing EET levels with t -AUCB promoted a dose dependent angiogenesis and migration in EPCs from AMI patients. Additionally, the t -AUCB dose dependently increased the expression of the angiogenic factors VEGF and HIF-α. Lastly, we provide evidence that these effects were PPARγ dependent. Conclusion The results demonstrate that the sEH inhibitor positively modulated the functions of EPCs in patients with AMI through the EETs–PPARγ pathway. The present study suggests the potential utility of sEHi in the therapy of ischemic heart disease.