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To evaluate the relation of proprotein convertase subtilisin-kexin type 9 (PCSK9) levels to coronary artery disease (CAD).A total of 1031 consecutive individuals (552 CAD and 479 controls) were prospectively enrolled. The associations of plasma PCSK9 levels with the incidence and severity of CAD were investigated. Further, mediator analysis was performed to detect the potential mechanisms of the associations.No difference in PCSK9 levels between CAD patients and controls was detected (median 224.75 versus 224.64 ng/mL, P0.05). However, the CAD group had higher PCSK9 levels than the control group when adjusting for the confounding factors (228.03 ± 1.01 versus 219.28 ± 1.02 ng/mL, P = 0.019). PCSK9 levels were also associated with the severity of CAD assessed by the Gensini score (GS) system (P for trend0.05). Logistic regression analysis showed that PCSK9 levels were associated with an increased CAD risk (OR 3.296 and 5.130 for the incidence and severity, respectively). Importantly, mediator analysis indicated that the effects of PCSK9 levels on CAD were mediated by lipid (around 20%) and inflammation (around 15%).PCSK9 levels were positively associated with the severity of CAD; the relatively important mechanisms including lipid and inflammation pathways were partly involved in this association.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been demonstrated to be involved in not only lipid metabolism but also glucose homeostasis. Glycated haemoglobin (HbA1c ) is a 'gold standard' for monitoring long-term glycaemic control. However, the correlation of plasma PCSK9 levels with HbA1c remains undetermined.We consecutively enrolled 805 subjects undergoing coronary angiography, including 176 patients with type 2 diabetes mellitus (T2DM) and 629 non-diabetic patients. The baseline characteristics were collected, and serum PCSK9 level was assessed by ELISA. Univariable regression analysis and multiple-variable regression analysis were used to examine the associations of PCSK9 with HbA1c . Furthermore, the HbA1c was compared across the tertiles of PCSK9 levels. And also, PCSK9 levels were compared in poorly controlled (HbA1c ≥ 7.0%) and well-controlled (HbA1c 7.0%) patients with T2DM.PCSK9 levels were positively correlated with low-density lipoprotein cholesterol in both T2DM and non-T2DM. Univariable regression analysis revealed a positive association between PCSK9 and HbA1c in patients with T2DM (β = 0.255, p = 0.001) but not in patients without diabetes (β = 0.061, p = 0.128). Multiple-variable regression analysis exhibited that PCSK9 was independently correlated with HbA1c in T2DM after adjustment for traditional atherosclerotic risk factors (β = 0.197, p = 0.020). Moreover, HbA1c level was higher in patients with the highest tertile of PCSK9 than that in the lowest tertile (p = 0.042). Additionally, higher levels of PCSK9 were found in poorly controlled group compared with the well-controlled group (p = 0.029).Data suggest a positive correlation of PCSK9 levels with HbA1c in patients with T2DM but not in patients without T2DM, indicating a potential role of PCSK9 in T2DM. Copyright © 2015 John WileySons, Ltd.

The objective of the study was to investigate the usefulness of serum lipoprotein(a) level in predicting the severity of new on-set coronary artery disease in type 2 diabetics. A total of 1254 new on-set, consecutive coronary artery disease patients were classified into two groups: diabetes group ( n = 380) and non-diabetes group ( n = 874). The relationship between serum lipoprotein(a) levels and the severity of coronary artery disease assessed by Gensini score was analysed. Data showed that the diabetes group had higher serum triglyceride and high sensitivity C-reactive protein levels but lower high-density lipoprotein cholesterol levels (all p

Background Previous studies including our group have indicated the effects of ezetimibe on increased plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) concentration, while the rapid expression in different organs and the potential molecular mechanisms for this impact have not been carefully evaluated. Methods Thirty rats were randomly divided into two groups (n = 15 for each), which were orally administrated with ezetimibe (10 mg/kg/day) or normal saline. Blood samples were obtained at day 3 after orally administration, and the PCSK9 levels were determined by ELISA. We further analyzed the mRNA expression of PCSK9, low-density lipoprotein receptor (LDLR), sterol regulator element-binding protein 2 (SREBP2), and hepatocyte nuclear factor 1 alpha (HNF-1α) by real-time PCR, as well as the protein expression by western blot, in liver, intestine and kidney respectively. Results Ezetimibe significantly increased plasma PCSK9 levels compared with control group, while there was no significant difference between the two groups with regard to lipid profile at day 3. Moreover, ezetimibe remarkably increased the expression of PCSK9, LDLR, SREBP2 and HNF-1α in liver. Enhanced expression of PCSK9, LDLR and SREBP2 protein were found in intestine and kidney, while no changes in the expression of HNF-1α were observed in intestine and kidney of rats with ezetimibe treatment. Conclusions The data demonstrated that ezetimibe increased PCSK9 expression through the SREBP2 and HNF-1α pathways in different organs, subsequently resulting in elevated plasma PCSK9 levels prior to the alterations of lipid profile in rats.

To investigate the association of resistin with proprotein convertase subtilisin–kexin type 9 (PCSK9) levels, another novel regulator of atherosclerosis, in the condition of coronary artery disease (CAD). We prospectively enrolled a total of 356 consecutive stable CAD patients who were not treated with lipid-lowering drugs in the present study. The baseline clinical characteristics were collected. Plasma PCSK9 and resistin levels were determined by ELISA. The relationship between plasma PCSK9 and resistin levels was investigated. Overall, plasma resistin exhibited a positive nonparametric correlation with PCSK9 levels (r = 0.123, p = 0.02). When the patients were classified into groups based on body mass index (BMI), the resistin correlated significantly to the PCSK9 levels in patients with BMI < 25 kg/m2 (r = 0.162, p = 0.026) but not in patients with BMI ≥ 25 kg/m2 (r = 0.087, p = 0.205). Multivariate regression analysis corroborated the relation between the PCSK9 and an elevated resistin level in patients with BMI < 25 kg/m2 independently of traditional parameters including age, sex, BMI, smoking, family history of CAD, systolic blood pressure, glucose, low density lipoprotein cholesterol, white blood cell, neutrophil to lymphocyte ratio, and high-sensitive C-reactive protein. Plasma resistin was positively related to PCSK9 levels in CAD patients with normal weight, suggesting that the circulating resistin might represent a link with PCSK9 level variations in CAD progression of normal body weight.

Both increased lipoprotein-associated phospholipase A2 (Lp-PLA2) concentrations and atherogenic lipoprotein subfractions have been shown to reflect unfavourable cardiovascular risk. However, the correlation between Lp-PLA2 and lipoprotein subfractions in patients with coronary artery disease (CAD) has not been assessed yet.A total of 324 consecutive subjects who were not treated with lipid-lowering drugs were enrolled (angiographically proven CAD: n = 253; non-CAD: n = 71). Plasma Lp-PLA2 concentrations were measured using ELISA. The low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions were determined by Lipoprint System.Plasma Lp-PLA2 concentrations were higher in patients with CAD compared with those without CAD (153.61 ± 78.73 vs. 131.41 ± 65.49 ng/ml, p = 0.028). The univariable correlation analysis revealed that Lp-PLA2 concentrations were positively correlated with the cholesterol concentrations of each LDL subfractions and the intermediate as well as small HDL subfractions, while negatively linked with the LDL particle size and large HDL-cholesterol (HDL-C) concentrations in CAD group. However, no similar results were observed in the non-CAD group. Furthermore, multivariable regression analysis was performed in patients with CAD and showed that plasma Lp-PLA2 concentrations were independently correlated with the cholesterol concentrations of each LDL subfractions [large LDL-cholesterol (LDL-C): β = 0.263, p0.001; intermediate LDL-C: β = 0.327, p0.001; small LDL-C: β = 0.135, p = 0.033] and small HDL-C (β = 0.133, p = 0.034).Lp-PLA2 concentrations were positively associated with all LDL subfractions and small HDL subfraction, suggesting an interaction between Lp-PLA2 and lipoprotein subfraction phenotypes in the status of CAD.

Background The relation of lipoprotein subfractions with stable coronary artery disease (CAD) has not been fully investigated in the Chinese Han population. Methods Four-hundred-and-thirteen consecutive patients without any lipid-lowering drug treatment were investigated. Patients were classified into two groups according to the angiographic results: CAD group (n=293) and non-CAD group (n=120). The high-density lipoprotein (HDL) and low-density lipoprotein (LDL) subfractions were analysed using the Quantimetrix Lipoprint system. Results The data showed that the large HDL-cholesterol (HDL-C) level, large HDL subfraction percentage, and mean LDL particle size were significantly lower, while the small HDL-C level and HDL subfraction percentage, intermediate and small LDL-cholesterol (LDL-C) levels, and LDL subfraction percentages were higher in the CAD group compared with those in the non-CAD group. Interestingly, our results suggested that the small HDL-C level and HDL subfraction percentage as well as mean LDL particle size were independently associated with the presence of CAD assessed by logistic regression analysis (OR=1.136, 95%CI=1.018-1.268, p=0.022; OR=1.076, 95%CI=1.021-1.134, p=0.007; OR=0.946, 95%CI=0.898-0.997, p=0.040; respectively). Conclusions Similar to previous Western population studies, our data suggested a clear association between the lipoprotein subfractions and stable CAD presented as higher small HDL subfraction and smaller mean LDL particle size in Chinese Han patients.

Background Recent data showed inconsistent association of high‐density lipoprotein cholesterol ( HDL ‐C) with cardiovascular risk in patients with different levels of low‐density lipoprotein cholesterol ( LDL ‐C) or intensive statin therapy. This study sought to determine the relationship of HDL ‐C with periprocedural myocardial injury following elective percutaneous coronary intervention ( PCI ) across a range of LDL ‐C levels, especially in patients with LDL ‐C dL . Methods and Results We enrolled 2529 consecutive patients with normal preprocedural cardiac troponin I ( cTnI ) who underwent elective PCI . The association between preprocedural HDL ‐C and periprocedural myocardial injury was evaluated across LDL ‐C levels, especially in patients with LDL ‐C dL . The HDL ‐C level was not predictive of periprocedural myocardial injury across the entire study cohort. However, among patients with LDL ‐C dL , a 1 mg/ dL increase in HDL ‐C was associated with a 3% reduced risk for postprocedural cTnI above 1×upper limit of normal ( ULN ) (odds ratio: 0.97; 95% CI : 0.95 to 0.99; P =0.004), a 3% reduced risk for postprocedural cTnI above 3× ULN odds ratio: 0.97; 95% CI : 0.95 to 0.99; P =0.022), and a 3% reduced risk for postprocedural cTnI above 5× ULN (odds ratio: 0.97; 95% CI : 0.95 to 0.99; P =0.017). The relation between plasma HDL ‐C level and risk of postprocedural cTnI elevation above 1× ULN , 3× ULN , and 5× ULN was modified by LDL ‐C level (all P for interaction Conclusions Higher HDL ‐C levels were associated with reduced risk of periprocedural myocardial injury only in patients with LDL ‐C dL .

Objective. To investigate the relationship between inflammatory markers and atherogenic lipoprotein subfractions.Methods. We studied 520 eligible subjects who were not receiving any lipid-lowering therapy. The inflammatory markers including white blood cell (WBC) count, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, erythrocyte sedimentation rate (ESR), and D-dimer were measured. A multimarker inflammatory index was developed. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) separation processes were performed using Lipoprint System.Results. In age- and sex-adjusted analysis, several inflammatory markers (WBC count, hs-CRP, fibrinogen, and ESR) were positively related to circulating non-HDL cholesterol and remnant cholesterol (p<0.05, all). Among lipoprotein subfractions, we observed a positive association of inflammatory markers with very low-density lipoprotein cholesterol, small LDL cholesterol, and LDL score (p<0.05, all). Meanwhile, a negative association was detected between inflammatory markers and mean LDL particle size (p<0.05) or large HDL cholesterol (p<0.05). Moreover, we found that the relationships between multimarker index quartiles and small LDL cholesterol, LDL score, and mean LDL particle size were slightly stronger in patients with CAD.Conclusions. Systemic inflammatory markers are positively correlated with small LDL cholesterol and LDL score while being negatively linked with mean LDL particle size and large HDL cholesterol, highlighting the potential contribution to increased cardiovascular risk.

Background Plasma PCSK9 levels was positively associated with low-density lipoprotein (LDL) cholesterol (LDL-C) and atherosclerosis, while PCSK9 may also be implicated in the metabolism of lipoprotein subfractions. The study was to examine the association of plasma PCSK9 with lipoprotein subfractions in patients with stable coronary artery disease (CAD). Methods A total of 281 consecutive, stable CAD patients who were not treated with lipid-lowering drugs were enrolled. The baseline clinical characteristics were collected, the plasma PCSK9 levels were determined using ELISA, and the LDL and high-density lipoprotein (HDL) subfractions were analyzed by Lipoprint System. The association of plasma PCSK9 levels with the lipoprotein subfractions was investigated. Results In the overall population, plasma PCSK9 levels were positively associated with the concentration of LDL-C, intermediate LDL-C, small LDL-C, and LDL score, while negatively correlated with mean LDL particle size. PCSK9 levels were positively associated with the concentration of HDL-C, intermediate HDL-C and small HDL-C. Multivariable regression analysis revealed that the plasma PCSK9 levels were significantly and independently associated with the concentration of intermediate LDL-C (β = 0.152, p = 0.013), small LDL-C (β = 0.179, p = 0.004), LDL score (β = 0.121, p = 0.043), and mean LDL particle size (β = -0.130, p = 0.035), while not HDL subfractions. Interestingly, when investigated in male and female patients separately, these relationships were only found in male but not in female, and the small HDL-C exhibited an association with PCSK9 levels in male patients (β = 0.149, p = 0.045). Conclusions PCSK9 levels were independently associated with the changes of lipoprotein subfractions, suggesting a potential interaction between PCSK9 and lipoprotein subfractions in CAD.

Background The proprotein convertase subtilisin/kexin type 9 (PCSK9) has been confirmed as a major factor regulating cholesterol homeostasis and has low-density lipoprotein receptor (LDLR) independent effects. In addition, the pathogenesis of acute myocardial infarction (AMI) involves lipids alteration and other acute phase responses. It remains unknown whether the PCSK9 expression is influenced by the impact of AMI. The present study aimed to investigate the changes of PCSK9 concentration using AMI rat model. Methods AMI (n = 6-8 at each time point) or sham operated (n = 6) adult male rats model were used. Whole blood and liver tissue were collected at 1, 3, 6, 9, 12, 24, 48, and 96 hour (h) post infarction. The plasma PCSK9 concentration was measured by ELISA and lipid profiles were measured by enzymatic assay. The liver mRNA levels of PCSK9, LDLR, sterol response element binding protein-2 (SREBP-2) and hepatocyte nuclear factor 1α (HNF1α) were measured by quantitative real-time PCR. Results The plasma PCSK9 concentration was increased from 12 h to 96 h (P

Serum uric acid (SUA) has been established to be highly associated with coronary artery disease (CAD) susceptibility and lipid metabolism, but the underlying mechanisms are unclear. Recently, lipoprotein subfractions have been proposed to be more valuable in CAD risk evaluation. Hence, we sought to investigate whether the relationship between SUA and CAD is partly mediated by lipoprotein subfractions.A total of 401 consecutive subjects undergoing coronary angiography were enrolled. The baseline clinical data including the SUA level and lipid profiles were collected. The lipoprotein subfractions were determined using the Lipoprint system.In the overall population, the upper SUA quintiles had significantly higher atherogenic lipid parameters and unbalanced lipoprotein subfractions especially higher small dense low-density lipoprotein-cholesterol (sdLDL-C) and lower large high-density lipoprotein-cholesterol (HDL-C) (p0.05). The levels of SUA and lipoprotein subfractions were dramatically different between male and female. After adjusting for traditional risk factors including gender, multivariate linear regression analysis suggested that SUA was positively associated with sdLDL-C (β=0.113, p=0.013) but negatively related to large HDL-C level (β=-0.152, p=0.002). Given the significant association of the SUA level with lipoprotein subfractions and incident CAD (adjusted OR=1.312, 95% CI 1.069-1.609, p=0.009), we performed the mediation analyses and found that 8.7-10.5% of the effect of SUA on CAD susceptibility was mediated by the increased sdLDL-C or decreased large HDL-C level (p0.05).The SUA level was proved to be associated with lipoprotein subfractions including sdLDL-C (positive) and large HDL-C (negative), which partly mediated the association between SUA and CAD susceptibility.

Objective. Statin treatment alone has been demonstrated to significantly increase plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels. The effect of policosanol combined with statin on PCSK9 is unknown.Methods. Protocol I: 26 patients with atherosclerosis were randomly assigned to receive either atorvastatin 20 mg/d or policosanol 20 mg/d + atorvastatin 20 mg/d for 8 weeks. Protocol II: 15 healthy volunteers were randomly assigned to either policosanol 20 mg/d or a control group for 12 weeks. Serum levels of PCSK9 were determined at day 0 and the end of each protocol.Results. Protocol I: atorvastatin 20 mg/d significantly increased serum PCSK9 level by 39.4% (256 ± 84 ng/mL versus 357 ± 101 ng/mL,P=0.002). However, policosanol 20 mg/d + atorvastatin 20 mg/d increased serum PCSK9 level by only 17.4% without statistical significance (264 ± 60 ng/mL versus 310 ± 86 ng/mL,P=0.184). Protocol II: there was a trend toward decreasing serum PCSK9 levels in the policosanol group (289 ± 71 ng/mL versus 235 ± 46 ng/mL,P=0.069).Conclusion. Policosanol combined with statin attenuated the statin-induced increase in serum PCSK9 levels. This finding indicates that policosanol might have a modest effect of lowering serum PCSK9 levels.

Proprotein convertase subtilisin-kexin type 9 (PCSK9) is a novel regulator of low-density lipoprotein (LDL) metabolism. Recently, small dense LDL (sdLDL) particles have been suggested to be a very atherogenic subspecies of LDL. To date, the association of sdLDL with PCSK9 is still unclear. The aim of the present study is to determine the association of sdLDL, as assayed by sdLDL-cholesterol (sdLDL-C), with PCSK9 in a cohort of subjects undergoing coronary angiography.Four hundred and ninety consecutive subjects were enrolled and classified into stable coronary artery disease (CAD) and non-CAD group. LDL separation was performed by Lipoprint System: 7 LDL subfractions were obtained and LDL score (% sdLDL) was calculated. The plasma PCSK9 levels were measured by ELISA. The data indicated that PCSK9 levels were significantly increased by sdLDL-C quartiles (p = 0.028). In age- and sex-adjusted analysis plasma sdLDL-C was positively correlated with PCSK9 levels (r = 0.157, p 0.01). To rule out the confounding effect of dyslipidemia, we performed the analysis in subjects with and without dyslipidemia separately. Interestingly, the positive correlation of sdLDL-C with PCSK9 was only significant in patients with dyslipidemia and stable CAD (r = 0.177, p 0.01). In a model adjusting for traditional risk factors including dyslipidemia, PCSK9 was an independent predictor of high sdLDL-C in CAD group (OR = 12.919, 95% CI 1.427-116.952) but not in non-CAD group.This study firstly demonstrated that plasma sdLDL-C was positively related to PCSK9 in patients with stable CAD, suggesting an interaction between sdLDL-C and PCSK9 in atherosclerotic coronary disease.

Objectives The aim of this study was to investigate the association of serum fibrinogen with cardiovascular events (CVE) in Chinese patients with type 2 diabetes mellitus (T2DM) and stable coronary artery disease (CAD). Design An observational study. Setting FuWai Hospital in Beijing, China. Participants A cohort of 1466 patients with T2DM and angiographic-proven stable CAD was evaluated. Outcome measures Baseline serum fibrinogen levels were measured and trisected into ‘low’, ‘middle’ and ‘high’. Their association with CVE was explored using Cox proportional hazard models. Results With 20.2 months (average) follow-up, 44 (3%) were lost to follow-up and 96 patients developed CVE. Compared with the patients without CVE, the ones who developed CVE had higher levels of fibrinogen. Univariable regression revealed a significant relation of fibrinogen to CVE (HR (HR) 1.25, 95% CI 1.06 to 1.47, p=0.010) per SD increase of fibrinogen at baseline. After adjusting for multiple established cardiovascular disease (CVD) risk factors, the association persisted (HR 1.30, 95% CI 1.02 to 1.66, p=0.037). Moreover, after adjusting for CVD risk factors, the HRs for middle-serum and high-serum fibrinogen concentration, using ‘low’ group as reference, were 1.23 (95% CI 0.69 to 2.20) and 2.20 (95% CI 1.11 to 3.36, p=0.049). Conclusions We first indicated that elevated fibrinogen level was independently associated with increased CVE in Chinese patients with T2DMand stable CAD.

a Center for Dyslipidemia and Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167 BeiLiShi Road, XiCheng District, Beijing 100037, China b Department of Cardiology, The Fifth Hospital of Wuhan & Affiliated Guangci Hospital of Wuhan University, Wuhan 430050, China

AIM To investigate the usefulness of the plasma big endothelin-1 (big ET-1) level in predicting the severity of new-onset stable angiography-proven coronary artery disease (CAD). METHODS A total of 963 consecutive stable CAD patients with more than 50% stenosis in at least one main vessel were enrolled. The patients were classified into the three groups according to the tertile of the Gensini score (GS, low GS ＜20, n=300; intermediate GS 20-40, n=356 and high GS ＞40, n=307), and the relationship between the big ET-1 level and GS was evaluated. RESULTS The plasma levels of big ET-1 increased significantly in association with increases in the GS tertile (p=0.007). A multivariate analysis suggested that the plasma big ET-1 level was an independent predictor for a high GS (OR=2.26, 95%CI: 1.23-4.15, p=0.009), and there was a positive correlation between the big ET-1 level and the GS (r=0.20, p=0.000). The area under the receiver operating characteristic curve (AUC) for the big ET-1 level in predicting a high GS was 0.64 (95% CI 0.60-0.68, p=0.000), and the optimal cutoff value for the plasma big ET-1 level for predicting a high GS was 0.34 fmol/mL, with a sensitivity of 62.6% and specificity of 60.3%. In the high-big ET-1 level group (≥0.34 fmol/mL), there were significantly increased rates of three-vessel disease (43.6% vs. 35.4%, p=0.017) and a high GS [31 (17-54) vs. 24 (16-44), p=0.001] compared with that observed in the low-big ET-1 level group. CONCLUSIONS The present findings indicate that the plasma big ET-1 level is a useful predictor of the severity of new-onset stable CAD associated with significant stenosis.

Aim: The usefulness of the white blood cell (WBC) count and neutrophil-to-lymphocyte ratio (NLR) in predicting the severity of stable coronary artery disease (CAD) has not been sufficiently evaluated, particularly based on strict coronary assessments. The aim of the present study was to investigate the WBC count and NLR in predicting the severity of angiographically proven CAD. Methods: A total of 2,976 CAD patients and 571 non-CAD patients were consecutively enrolled, and the CAD patients were classified into the three groups according to the tertile of the Gensini score (GS, low GS＜18, n=989; intermediate GS 18-41, n=995 and high GS＞41, n=992). The efficacy of the WBC count and NLR in predicting the risk and severity of CAD as well as the correlations between these markers and the GS were analyzed. A receiver operating characteristic (ROC) curve analysis was also performed. Results: The NLR was found to be an independent predictor of both the presence of CAD (OR=1.18, 95%CI: 1.09-1.27, p=0.009) and a high GS (OR=1.10, 95%CI: 1.01-1.16, p=0.032). In addition, there were mild positive correlations between the GS and the NLR, WBC and proportions of neutrophils and monocytes. In the ROC curves analysis, the NLR was found to have the largest area under the curve (AUC=0.63, 95%CI: 0.59-0.67, p=0.000), with an optimal cut-off value of 2.04 (sensitivity: 62.1%, specificity: 54.8%) for predicting a high GS. Conclusions: The NLR is a valuable independent predictor of the severity of CAD assessed according to the GS. In particular, an NLR of ＞2.04 indicates a higher risk of CAD and greater severity of CAD lesions. J Atheroscler Thromb, 2014; 21:000-000.

To investigate the effects of Hedan Tablet (荷丹片) on serum lipid profile, proprotein convertase subtilisin/kexin type 9 (PSCK9) and high-density lipoprotein (HDL) subfractions in patients with hyperlipidemia. Thirty-seven patients with hyperlipidemia were randomized to treatment with Hedan Tablet 4.38 g/day as Hedan group (18 cases) or placebo (19 cases) as control group for 8 weeks. The lipid profile, PCSK9 and HDL subfractions were determined at day 0 and week 8 in both groups respectively. Hedan treatment for 8 weeks mildly decreased serum low-density lipoprotein cholesterol (LDL-C) levels, while no changes were found in total cholesterol (TC), triglycerides (TG) and PCSK9 concentrations. Furthermore, Hedan treatment increased the concentration of large high-density lipoprotein cholesterol (HDL-C) and the percentage of large HDL subfraction, while decreased the concentration of small HDL-C and the percentage of small HDL subfraction without changing serum HDL-C levels in patients with hyperlipidemia. Hedan treatment of 4.38 g per day for 8 weeks could confer a favorable effects on serum LDL-C concentration as well as HDL subfractions.

Objective : Although the study on the relationship between ABO blood groups and coronary atherosclerosis has a long history, few data is available regarding ABO to severity of coronary atherosclerosis in a large cohort study. Therefore, the present study aimed to investigate the relation of the ABO blood groups to the severity of coronary atherosclerosis assessed by Gensini score (GS) in a large Chinese cohort undergoing coronary angiography. Methods : A total of 2919 consecutive patients undergoing coronary angiography were enrolled, and their baseline characteristics and ABO blood groups were collected. The GS was calculated as 1st tertile (0–10), 2nd tertile (11–36), 3rd tertile (>36) according to angiographic results. The relation of the ABO blood groups to GS was investigated. Results : The frequency of blood group A was significantly higher in the upper GS tertiles (24.4% vs. 28.2% vs. 29.5%, p = 0.032). Multivariable linear regression analysis revealed that blood group A was independently associated with GS ( β = 0.043, p = 0.017). Likewise, multivariable logistic regression analysis showed that group A remained significantly associated with mid-high GS (OR = 1.44, 95% CI 1.16–1.80, p = 0.001), and the group O was showed as a protective factor (OR = 0.77, 95% CI = 0.65–0.92, p = 0.004). Conclusion : In this large Chinese cohort study, the data indicated that there was an association between ABO blood groups and the severity of coronary atherosclerosis. Moreover, the blood group A was an independent risk factor for serious coronary atherosclerosis.

The exact role of different high-density lipoprotein (HDL) subfractions in the pathogenesis of coronary artery disease (CAD) has not yet been fully explored. The aim of the present study was to examine the relationship between HDL subfractions and the severity of CAD in patients without statin therapy.A total of 382 consecutive patients (mean: 55.36 ± 11.30 years of age) who underwent coronary angiography from angina-like chest pain were investigated. Patients were classified into 2 groups according to the angiographic results: a CAD group (n = 283) and a control group (n = 99). The distribution of HDL subfractions was analyzed using a Quantimetrix Lipoprint HDL system. CAD severity was measured by Gensini score (GS).Compared with the control group, HDL-cholesterol (HDL-C), large HDL-C level, and the large HDL subfraction percentages in the CAD group were significantly lower (P = .002, P.001, P.001, respectively). Meanwhile, a small HDL-C level and the percentage of small HDL subfraction were significantly higher (P = .003, P.001, respectively). Correlation analysis showed that the percentage of a large HDL subfraction was negatively correlated with GS (β = -0.191, P = .005), whereas the percentage of a small HDL subfraction positively correlated with GS (β = 0.145, P = .023) in patients with CAD.Small HDL subfraction was associated with the presence of CAD, whereas the percentage of large HDL and small HDL subfraction was negatively and positively associated with the severity of CAD, respectively.

It has been shown that alkaline phosphatase (ALP) is a reliable marker for cardiovascular events and mortality. However, there is no data available regarding the association of ALP with isolated coronary artery ectasia (CAE). The aim of the present study was to assess the serum ALP activity in isolated CAE.Seventy-nine patients with isolated CAE (59 males; mean age, 52 ± 12 years) and 88 age- and gender-matched normal subjects (73 males; mean age, 52 ± 7 years) were enrolled. Baseline characteristics were recorded in both groups and serum ALP activity were compared between the two groups.Patients with angiography-proved isolated CAE had significantly higher serum ALP activity compared with angiographic normal controls (72.41 ± 29.97 vs. 59.27 ± 14.46, p0.001). In the multivariate analysis, increased ALP (OR = 1.037, 95% CI 1.017-1.057, p0.001) were independent predictors for the presence of isolated CAE. A cut-off of ≥ 66.5 U/L of ALP activity measured on admission had a 60.8% sensitivity and 75.0% specificity in predicting isolated CAE by receiver operating characteristic (ROC) curve analysis.Our data firstly demonstrated that serum ALP activity, a readily available clinical laboratory value, was associated with the presence of isolated CAE.

Background The role of triglyceride (TG) in predicting the outcomes in diabetic patients with coronary artery disease (CAD) has not been well investigated. Methods A total of 329 cases with stable angina pectoris (SAP) were prospectively enrolled and followed up for an average of 12 months. They were classified into the two groups according to the cut-off values of predicting early outcome of fasting TG level (low group

Lower levels of low-density lipoprotein cholesterol (LDL-C) are associated with less cardiovascular risk in patients with coronary artery disease.To assess whether lower preprocedural LDL-C levels are associated with less risk of periprocedural myocardial injury in patients undergoing elective percutaneous coronary intervention (PCI).We enrolled 2529 consecutive patients with normal preprocedural cardiac troponin I (cTnI) who successfully underwent elective PCI. The association between preprocedural LDL-C levels and peak cTnI levels within 24 hours after PCI was evaluated.Preprocedural LDL-C levels were correlated to postprocedural cTnI levels (r = 0.059, P = .003). In the multivariable model, preprocedural LDL-C levels between 70 and 99 mg/dL were associated with less risk of postprocedural cTnI elevation above 1 × upper limit of normal (ULN) (odds ratio [OR]: 0.804; 95% confidence interval [CI]: 0.663-0.975; P = .027) up to 15 × ULN (OR: 0.709; 95% CI: 0.530-0.949; P = .021) compared with preprocedural LDL-C levels ≥100 mg/dL. Moreover, preprocedural LDL-C levels70 mg/dL were more strongly associated with less risk of postprocedural cTnI elevation above 1 × ULN (OR: 0.736; 95% CI: 0.584-0.927; P = .009) up to 15 × ULN (OR: 0.655; 95% CI: 0.452-0.950; P = .026).Lower preprocedural LDL-C levels were associated with less risk of periprocedural myocardial injury in patients undergoing elective PCI.

Background An emerging data suggested a significant impact of statins on PCSK9 concentration, while the rapid impacts of other lipid-lowering drugs such as ezetimibe and xuezhikang alone or in combination on PCSK9 and lipid profile have not been assessed. This study aims to investigate whether an enhanced PCSK9 concentration by single or combined therapy of lipid-lowering drugs currently used precedes the changes of lipid profile in rats. Methods Sixty-three rats were randomly divided into six groups and orally administrated with placebo (N = 13), ezetimibe 10 mg/kg daily, Xuezhikang 1200 mg/kg daily, ezetimibe 10 mg/kg plus Xuezhikang 1200 mg/kg daily, pitavastatin 10 mg/kg daily or pitavastatin 10 mg/kg plus ezetimibe 10 mg/kg daily for 3 days (N = 10 for each group respectively). Blood samples were obtained at day 3 after orally administration. Plasma PCSK9 levels were determined by ELISA and lipid profile were measured by enzymatic assay. Results Ezetimibe, Xuezhikang and pitavastatin alone and Xuezhikang plus ezetimibe as well as pitavastatin plus ezetimibe increased PCSK9 levels by 124%, 56%, 111%, 63% and 204% respectively (p 0.05). Conclusions Elevated PCSK9 concentration by ezetimibe, Xuezhikang and pitavastatin alone or in combination was found prior to the alterations of lipid profile in rats. Combination of Xuezhikang and ezetimibe significantly attenuated increase in PCSK9 compared to ezetimibe plus pitavastatin, suggesting that the former combination may be better than the latter in future clinical application.

Background Fibrinogen is a coagulation/inflammatory biomarker strongly associated with atherogenesis. However, no data is currently available regarding the association of fibrinogen level with the presence and severity of new-onset coronary atherosclerosis assessed by Gensini score (GS), particularly in Han Chinese with a large sample size. Methods and Results We studied 2288 consecutive, new-onset subjects undergoing coronary angiography with angina-like chest pain. Clinical and laboratory data were collected. Coronary stenotic lesions were considered to be the incidence of coronary atherosclerosis. The severity of coronary stenosis was determined by the GS system. Data indicated that patients with high GS had significantly elevated fibrinogen level (p

Recent studies have suggested that proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with atherosclerosis and plays a potential role in inflammation. However, the correlation between PCSK9 and white blood cell count (WBCC) has not yet been assessed. The objective of the present study was to examine the association of the WBCC and its subset counts with plasma PCSK9 levels in patients with stable coronary artery disease (CAD).In this cross-sectional study, a total of 251 consecutive, stable CAD patients who were not treated with lipid-lowering drugs were enrolled at our center between October 2012 and October 2013. The baseline clinical characteristics were collected, and the plasma PCSK9 levels were determined using ELISA. The associations of plasma PCSK9 levels with the WBCC and its subsets were investigated.In the overall population, plasma PCSK9 levels were positively associated with the WBCC (r = 0.167, p = 0.008). Multivariable regression analysis revealed that the plasma PCSK9 levels were significantly and independently associated with the WBCC (β = 0.217, p0.001) and its subsets (neutrophil β = 0.152, p0.05; lymphocyte β = 0.241, p0.001). However, the relationships between PCSK9 and WBCC and its subsets remained significant in men (WBCC r = 0.234, p = 0.001; neutrophil r = 0.181, p = 0.014; lymphocyte r = 0.226, p = 0.002) but were not significant in women when the analysis was performed based on gender.These data demonstrate that the plasma PCSK9 levels are independently associated with the WBCC and its subsets, suggesting a potential interaction between PCSK9 and chronic inflammation in patients with CAD.

Homozygous familial hypercholesterolemia (HoFH) is a rare, inherited metabolic disease, caused by low-density lipoprotein (LDL) receptor abnormality, consequently leading to an increase of serum levels of LDL cholesterol (LDL-C). Clinically, this disease is characterized by the deposition of LDL-C in skin, tendons, and arterial wall. Children with HoFH develop significant coronary artery disease (CAD) in the first decade of life and frequently die of myocardial infarction (MI) before 20 years of age.An 8-year-old boy with a diagnosis of acute MI on January 15, 2012 was admitted to our hospital for further evaluation of the potential cause and treatment. He had severe hypercholesterolemia for the past several years and showed typical signs of FH. Laboratory work-up excluded secondary causes of hypercholesterolemia and a diagnosis of HoFH was made after assessing the lipid profiles of his parents and his relatives. After careful consideration, he was prescribed a combination regime of lipid-lowering therapy. The plasma pro-protein convertase subtilisin/kexin type 9 (PCSK9) levels were also evaluated for him and his family members.His total cholesterol (TC) was 18.96 mmol/L and both parents had hypercholesterolemia (TC of mother: 7.46 mmol/L and father: 8.74 mmol/L). The plasma level of PCSK9 of the patient was significantly higher than his parents and his uncles and this pattern was similar with the level of their lipid profile. Importantly but not surprisingly, his serum lipid profile was not significantly improved by concomitant use of rosuvastatin 10 mg and ezetimibe 10 mg daily for one month, even a double dose of rosuvastatin and ezetimibe 10 mg daily for another month.The present case may have an important clinical implication for future investigation regarding the relation of HoFH to statin and PCSK9.

Background Obesity is associated with unfavorable alternations in plasma lipid profile and a broad spectrum of cardio-metabolic disorders. Proprotein convestase subtilisin kexin type 9 (PCSK9) is a novel circulating protein that promotes hypercholesterolemia by decreasing hepatic low lipoprotein density receptor (LDLR) protein. However, the relationship between PCSK9 concentration and lipid profile in an obesity condition has less been investigated. Objective To examine the changes of plasma PCSK9 concentration in a rat model fed with high fat diet (HFD) and its correlation to lipid profile, body weight and ageing. Methods Twenty male Sprague Dawley (SD) rats were divided into two groups, control group (fed with normal pellet for 4 weeks), and high-fat diet group (fed with 3% cholesterol enrich diet for 4 weeks). Blood samples of rats were obtained before and at days 14, 21, and 28 in both groups. The body weight, plasma metabolic parameters (glucose, lipid profile) and PCSK9 were determined at indicated time points. Results The body weights were significantly increased in rats fed with HFD compared to that in rats with normal pellets at day 28. Additionally, total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) levels in rat fed with HFD were also higher than that in rats fed with control diet while decreased high density lipoprotein cholesterol (HDL-C) levels were found in rats with HFD at day 28. More interesting, there were no differences of plasma PCSK9 concentrations as well as hepatic expression of LDLR between the two groups at day 28. Conclusions Although the body weight and LDL-C were significantly increased in rats fed with HFD at 4 weeks, there were no differences of changes in plasma PCSK9 concentration and LDLR expression of liver tissue in both groups at baseline and day 28, suggesting that dyslipidemia in the rat model with HFD appears not to be associated with PCSK9-LDLR pathway but ageing.

Background Both coronary artery disease (CAD) and diabetes mellitus (DM) are associated with inflammation. However, whether and which leukocytes can predict the presence and extent of CAD in patients with DM has not been investigated. The aim of the present study was to examine the association of leukocyte and its subsets counts with the severity of CAD in patients with DM. Methods and Findings Three hundred and seventy-three diabetic patients who were scheduled for coronary angiography due to typical stable angina pectoris were enrolled in this study. They were classified into the three groups according to tertiles of Gensini score (GS, low group 28, n = 121). The relationship between the leukocyte and its subsets counts with the severity of CAD were evaluated. The data indicated that there were significant correlations between leukocyte and neutrophil counts with GS (r = 0.154 and 0.156, respectively, all P28 points) was 5.0×109 cells/L in diabetic patients.

OBJECTIVE: An elevated red cell distribution width has been recognized as a predictor of various cardiovascular diseases. Slow coronary flow syndrome is an important angiographic clinical entity with an unknown etiology. This study aimed to examine the relationship between red cell distribution width and the presence of slow coronary flow syndrome. METHODS: In total, 185 patients with slow coronary flow syndrome and 183 age- and gender-matched subjects with normal coronary flow (controls) were prospectively enrolled in this study. Red cell distribution width and C-reactive protein were measured upon admission, and the results were compared between the patients with slow coronary flow syndrome and normal controls. RESULTS: Red cell distribution width levels were significantly higher in the patients with slow coronary flow syndrome than the normal controls. Moreover, the data showed that the plasma C-reactive protein levels were also higher in the patients with slow coronary flow syndrome than in the normal controls. In addition, a multivariate analysis indicated that C-reactive protein and red cell distribution width were the independent variables most strongly associated with slow coronary flow syndrome. Finally, the red cell distribution width was positively correlated with C-reactive protein and mean thrombosis in the myocardial infarction frame counts of the patients with slow coronary flow syndrome. CONCLUSION: The data demonstrated that red cell distribution width levels are significantly higher and strongly positively correlated with both C-reactive protein and thrombosis in the myocardial infarction frame counts of patients with slow coronary flow syndrome. These findings suggest that red cell distribution width may be a useful marker for patients with slow coronary flow syndrome.

It has been reported that increased red blood cell width (RDW) is a marker associated with the presence and adverse outcomes of various cardiovascular diseases. The aim of the present study was prospectively evaluate the severity of coronary artery disease (CAD) and RDW in a large Chinese cohort.A total of 677 consecutive individuals who underwent coronary angiography due to the presence of angina-like chest pain and/or positive treadmill exercise test were enrolled in this study. All patients received coronary angiography and were then divided into two groups based on the results of coronary angiography (CAD group (n = 499) and control group (n = 178)). The clinical information including classical CAD risk factors and RDW were analyzed to identify their relationship to CAD. The severity of CAD was evaluated by Gensini score and its relationship with RDW was also analyzed.Patients with angiographic CAD had significantly elevated RDW levels compared with controls ((12.95 ± 0.77)% vs. (12.73 ± 0.83)%, P = 0.001). There was a significant positive correlation between RDW and the Gensini score (r = 0.37, P0.001). In multivariate Logistic regression analysis, RDW was demonstrated to be an independent predictor for both angiographic CAD (OR = 1.34, 95%CI: 1.02 - 1.77, P0.05) and for a higher Gensini score (13, OR = 2.23, 95%CI: 1.62 - 3.08, P0.001). In a receiver operating characteristic (ROC) curve analysis, an RDW value of 12.85% was identified as an effective cut-point in predicting the presence or absence of CAD with a sensitivity of 50.0% and a specificity of 65.2%.RDW is associated with both presence of CAD and the severity of coronary stenosis, suggesting that it might be a readily available marker for the prediction of CAD and its severity.

BACKGROUND: Cardiac syndrome X (CSX) is a condition characterized by chest pain with normal coronary arteries. However, its pathogenesis has not fully been understood yet. Red blood cell distribution width (RDW) has recently been suggested as a marker of acute and chronic cardiovascular diseases, while no data is available in patients with CSX. METHODS: One hundred and twenty consecutive patients with CSX and 102 normal controls were prospectively enrolled in this study. Blood samples were drawn from all individuals for measuring RDW and high-sensitivity C-reactive protein (CRP). The baseline data were compared between patients with CSX and normal controls. RESULTS: The RDW levels were significantly higher in patients with CSX than that in those with normal controls (13.1 ± 2.1 versus 12.3 ± 1.8, p = 0.011). Moreover, the data showed that the levels of plasma CRP were marked higher in patients with CSX than those that were observed in normal controls (CRP: 2.8 ± 2.2 mg/L versus 2.0 ± 1.7 mg/dl, p = 0.014). In addition, the multivariate analysis indicated that peripheral monocyte cell, CRP and RDW were the independent variables most strongly associated with CSX. In a receiver operating characteristic (ROC) curve analysis, we found that an RDW value of 12.8% was used as an effective cut-point in the segregation of the presence or absence of cardiac syndrome X, a sensitivity of 52.0% and a specificity of 65.4% were obtained. Finally, correlation analysis suggested that there was positive correlation between plasma levels of CRP and RDW levels (n = 120, γ = 0.381, P = 0.013). CONCLUSIONS: The present study, for the first time, demonstrated that elevated RDW and CRP levels were independently associated with the presence of CSX.

High-density lipoprotein (HDL) is highly heterogeneous in its size and composition. Till now, the link of HDL subfractions to coronary risk is less clear. We aimed to investigate the associations of HDL subfractions with traditional risk factors (RFs), coronary severity, and outcomes in a cohort of nontreated patients with stable coronary artery disease (CAD). We prospectively enrolled 591 eligible patients. Baseline HDL subfractions were separated by Lipoprint system. HDL subfractions (large, medium, and small) and HDL-cholesterol (HDL-C) levels were dichotomized into low and high group according to the 50 percentile. Coronary severity was evaluated by SYNTAX, Gensini, and Jeopardy scoring systems. Patients were followed up annually for major adverse cardiovascular events (MACEs). Cox proportional hazards' models were used to evaluate the risk of HDL subfractions on MACEs. Patients with high large HDL-C levels had a decreased number of RFs. Significantly, large HDL-C levels were negatively associated with coronary severity assessed by SYNTAX and Gensini score (both P 0.05). In particular, the multivariate Cox-proportional hazards model revealed that high large HDL-C was associated with lower MACEs risk (hazard ratio [95% confidence interval] 0.531 [0.295-0.959]) independent of potential confounders. Higher large HDL-C but not medium, small, or total HDL-C is associated with lower cardiovascular risk, highlighting the potential beneficial of HDL subfractionation.

ObjectiveTo investigate the influence and mechanism of salvianolic acid B (SalB) on apoptosis inhibition in rat bone marrow-derived mesenchymal stem cells (BMSCs) induced by hypoxia and serum deprivation (hypoxia/SD).MethodsSalB concentration of 0.1, 1, 10 or 100 mg/L (drug groups) were investigated for their ability to inhibit apoptosis in rat BMSCs. BMSCs in both the apoptosis model and drug groups were cultured under hypoxic conditions for 6 h, after which cell apoptosis and change in mitochondrial membrane potential (MMP) were detected using flow cytometry. Activation of caspase-3 was detected using western blot analysis.ResultsHypoxia/SD induced apoptosis in rat BMSCs. The early apoptosis rate was lower in the drug groups compared to the apoptosis model group (P

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is suggested as a novel factor associated with coronary artery disease (CAD). However, few studies have comprehensively evaluated plasma PCSK9 with cardiovascular risk till now. Hence, we aimed to prospectively investigate the association between baseline PCSK9 and cardiovascular risk graded with number of risk factors (RFs), coronary severity, and outcomes in patients with stable CAD.Baseline characteristics and biomarkers were measured in 616 consecutive, nontreated patients with stable CAD. Coronary severity was measured using SYNTAX, Gensini, and Jeopardy scoring systems. Patients were then received treatment and followed for a median of 17 months. The primary endpoints were cardiac death, stroke, myocardial infarction (MI), post-discharge revascularization, or unstable angina (UA).Overall, follow-up data were obtained from 603 patients. A total of 72 (11.9%) patients presented with at least 1 major adverse cardiovascular event (MACE) (4 cardiac deaths, 4 strokes, 6 MIs, 28 revascularizations, and 30 UAs). At baseline, PCSK9 was increased with an increasing number of RFs and positively associated with coronary severity scores (P

Supplemental Digital Content is available in the text, ABO blood type locus has been reported to have ethnic difference and to be a pivotal genetic determinant of cardiovascular risk, whereas few prospective data regarding the impact on cardiovascular outcomes are available in a large cohort of patients with angiography-proven coronary artery disease, especially from the Chinese population. The objective of this study was to assess the prognostic role of blood type in future cardiovascular events (CVEs) in Chinese Han patients undergoing coronary angiography. The population of this prospective cohort study consisted of 3823 eligible patients, and followed annually to capture all CVEs. Baseline characteristics and ABO blood type were obtained. Cox proportional hazards models were used to evaluate the risk of ABO blood type on CVEs. New CVEs occurred in 348 patients [263 (10.3%) non-O and 85 (7.8%) O] during a median period of 24.6 months follow-up. Significantly, non-O blood group was related to the presence and severity of coronary atherosclerosis and several risk factors including inflammatory markers. The log-rank test revealed that there was a significant difference between non-O and O blood groups in event-free survival analysis (P = 0.026). In particular, the Cox proportional hazards models revealed that non-O blood type was associated with increased CVEs risk [hazard ratio (95% confidence interval) 1.320 (1.033–1.685)], even after adjusting for potential confounders [adjusted hazard ratio (95% confidence interval) non-O: 1.289 (1.003–1.656); A: 1.083 (0.797–1.472); B: 1.481 (1.122–1.955); AB: 1.249 (0.852–1.831), respectively]. Non-O blood type is associated with future CVEs in Chinese Han patients undergoing coronary angiography.

The exact mechanisms of hypertension contributing to atherosclerosis have not been fully elucidated. Although multiple studies have clarified the association with low-density lipoprotein (LDL) subfractions, uncertainty remains about its relationship with high-density lipoprotein (HDL) subfractions. Therefore, we aimed to comprehensively determine the relationship between distribution of HDL subfractions and hypertensive status. A total of 953 consecutive subjects without previous lipid-lowering drug treatment were enrolled and were categorized based on hypertension history (with hypertension [n = 550] or without hypertension [n = 403]). Baseline clinical and laboratory data were collected. HDL separation was performed using the Lipoprint System. Plasma large HDL-cholesterol (HDL-C) and large HDL percentage were dramatically lower whereas the small HDL-C and small HDL percentage were higher in patients with hypertension (all P 0.05; combination vs single drug therapy, P > 0.05). However, the blood pressure well-controlled patients have significantly lower small HDL subfraction (P

To establish a reverse remodeling heart model in rats and observe collagen and TGF-β expression and relevant microRNAs changes during reverse remodeling.Lewis rats were divided into four groups including sham (NL, n = 10), abdominal aortic constriction (AAC, n = 10), heterotopic transplantation of abdominal aortic constriction (AAC-HT, n = 9) and heterotopic transplantation of normal heart (HT, n = 8). Left ventricular wall thickness and LV cavity were measured by echocardiography. The cardiomyocyte cross-sectional area (CSA) was determined on HE stained sections. Immunohistochemical and qRT-PCR were used to detect collagen and TGF-β expressions. miRNAs were detected by MicroRNA microarray.Heart weight, left ventricular wall thickness and CSA were significantly increased in AAC hearts compared to those in the NL and AAC-HT hearts. The collagen and TGF-β were increased in AAC hearts and further increased in AAC-HT hearts. miRNA microarray evidenced more than two folds changes on 82 miRNAs compared to NL (10 in AAC, 32 in AAC-HT and 40 in HT).Rat abdominal aortic constriction and heterotopic transplantation could be used as a reverse remodeling heart model and significant collagen and TGF-β as well microRNA expression changes were evidenced in this model.

1. Icariin is a major constituent of flavonoids derived from the Chinese medicinal herb Epimedium revicornum Maxim. The aim of the present study was to investigate whether icariin has protective effects on learning ability and memory in a rat model of chronic cerebral hypoperfusion. 2. Chronic cerebral hypoperfusion was induced by permanent ligation of the common carotid artery in Wistar rats for 4 months. One month after permanent artery occlusion, rats were adminitered icariin at doses of 0, 30, 60 or 120 mg/kg per day, p.o., for 3 months. Neurobehavioural and neurobiochemical parameters were examined to evaluate the effects of icariin on cognitive deficits induced by chronic cerebral hypoperfusion. 3. The Morris water maze test revealed that learning ability and memory were severely impaired in untreated rats, but were significantly improved in icariin-treated rats. Icariin treatment also ameliorated chronic cerebral hypoperfusion-induced oxidative stress in the brain, as evidenced by reduced malondialdehyde formation and maintained superoxide dismutase activity. In addition, the decreased hippocampal levels of acetylcholine, acetylcholinesterase and choline acetyltransferase associated with chronic cerebral hypoperfusion were significantly prevented by icariin treatment. 4. In conclusion, icariin protects against cognitive deficits induced by chronic cerebral hypoperfusion in rats. These effects appear to be mediated through its anti-oxidant effects, as well as its effects on the circulatory and cholinergic systems.

To investigated the effect of lovastatin on hypoxia and serum deprivation (Hypoxia/SD) induced rat MSCs apoptosis in vitro and associated signaling pathway changes.MSCs were isolated from Sprague-Dawley rats. The anti-apoptotic effects of lovastatin were detected using Hoechst33342 and annexin V-FITC/PI binding assay by Flow cytometric analysis. The phosphorylation of Akt and ERK1/2, the cytochrome C and the cleaved caspase-3 were detected by Western blot.Lovastatin (0.01 - 1 micromol/L) significantly reduced Hypoxia/SD-induced MSCs apoptosis and increased Akt phosphorylation, reduced caspase-3 activation and cytochrome c release from mitochondria to cytosol in a time dependent manner. These effects could be significantly blocked by both PI3K inhibitor, LY294002 and ERK1/2 inhibitor, U0126.Our results showed that lovastatin protects MSCs from Hypoxia/SD-induced apoptosis via activating PI3K/Akt and ERK1/2 signaling pathways suggesting a potential role of statins as an adjunct therapeutic agent during transplanting MSCs into damaged heart after myocardial infarction.

Cell therapy with bone marrow-derived mesenchymal stem cells (MSCs) has been shown to have great promises in cardiac repair after myocardial infarction. However, poor viability of transplanted MSCs in the infracted heart has limited the therapeutic efficacy. Our previous studies have shown in vitro that rat MSCs undergo caspase-dependent apoptosis in response to hypoxia and serum deprivation (Hypoxia/SD). Recent findings have implicated statins, an established class of cholesterol-lowering drugs, enhance the survival of cells under various conditions. In this study, we investigated the effect of lovastatin on rat MSCs apoptosis induced by Hypoxia/SD, focusing in particular on regulation of mitochondrial apoptotic pathway and the survival signaling pathways. We demonstrated that lovastatin (0.01-1 microM) remarkably prevented MSCs from Hypoxia/SD-induced apoptosis through inhibition of the mitochondrial apoptotic pathway, leading to attenuation of caspase-3 activation. The loss of mitochondrial membrane potential and cytochrome-c release from mitochondria to cytosol were significantly inhibited by lovastatin. Furthermore, the antiapoptotic effect of lovastatin on mitochondrial apoptotic pathway was effectively abrogated by both PI3K inhibitor, LY294002 and ERK1/2 inhibitor, U0126. The phosphorylations of Akt/GSK3 beta and ERK1/2 stimulated by lovastatin were detected. The activation of ERK1/2 was inhibited by a PI3K inhibitor, LY294002, but U0126, a ERK1/2 inhibitor did not inhibit phosphorylation of Akt and GSK3 beta. These data demonstrate that lovastatin protects MSCs from Hypoxia/SD-induced apoptosis via PI3K/Akt and MEK/ERK1/2 pathways, suggesting that it may prove a useful therapeutic adjunct for transplanting MSCs into damaged heart after myocardial infarction.

The pharmacological actions of Uncaria alkaloids, rhynchophylline and isorhynchophylline extracted from Uncaria rhynchophylla Miq Jacks were reviewed. The alkaloids mainly act on cardiovascular system and central nervous system including the hypotension, brachycardia, antiarrhythmia, and protection of cerebral ischemia and sedation. The active mechanisms were related to blocking of calcium channel, opening of potassium channel, and regulating of nerve transmitters transport and metabolism, etc.

Background Red cell distribution width (RDW) has been recognized as a novel marker for several cardiovascular diseases. The aim of this study was to evaluate the association between RDW levels and the presence of isolated coronary artery ectasia (CAE). Methods We studied 414 subjects including 113 patients with isolated CAE (Group A), 144 patients with coronary artery disease (CAD, group B) and 157 angiographically normal controls (group C). Baseline clinical characteristics and laboratory findings including RDW were compared among three groups. Results The levels of RDW were significantly higher in group A and B compared with that in group C (12.97 ± 1.4 and 12.88 ± 1.0 vs 12.34 ± 0.9, p = 0.020) while no difference was found between CAE and CAD (p = 0.17). Additionally, the levels of CRP were also higher in patients with CAE and CAD compared with normal controls (0.26 ± 0.14 mg/L, 0.31 ± 0.27 mg/L vs 0.20 ± 0.06 mg/L, p = 0.04). The multivariate analysis indicated that RDW and CRP were the independent variables most strongly associated with the presence of isolated CAE and CAD. There was a positive correlation between levels of RDW and CRP in patients with isolated CAE (γ=0.532, p = 0.001). Conclusions Our data suggested that RDW may be a useful marker and independent predictor for the presence of isolated CAE.