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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 1a (HNF1a) were measured by quantitative real-time PCR. Results: The plasma PCSK9 concentration was increased from 12 h to 96 h (P < 0.05 vs. control). Paralleled with the enhanced plasma PCSK9 concentration, the hepatic PCSK9 mRNA expression was up-regulated by 2.2-fold at 12 h and 4.1-fold at 24 h. Hepatic mRNA levels of LDLR, SREBP-2 and HNF1a were all increased and lipid profiles underwent great changes at this acute period. Conclusions: We firstly demonstrated that PCSK9 was transiently up-regulated in the acute period of AMI, which is also driven by transcriptional factors, SREBP-2 and HNF1a, suggesting that the role of PCSK9 in myocardial injury may be needed further study. [ABSTRACT FROM AUTHOR]

Background Lower levels of low-density lipoprotein cholesterol (LDL-C) are associated with less cardiovascular risk in patients with coronary artery disease. Objectives 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). Methods 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. Results 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 x upper limit of normal (ULN) (odds ratio [OR]: 0.804; 95% confidence interval [CI]: 0.663-0.975; P = .027) up to 15 x 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 levels <70 mg/dL were more strongly associated with less risk of postprocedural cTnI elevation above 1 x ULN (OR: 0.736; 95% CI: 0.584-0.927; P = .009) up to 15 x ULN (OR: 0.655; 95% CI: 0.452-0.950; P = .026). Conclusions Lower preprocedural LDL-C levels were associated with less risk of periprocedural myocardial injury in patients undergoing elective PCI. [ABSTRACT FROM AUTHOR]

Background Glycosylated hemoglobin A1C (HbA1c) has been widely recognized as a marker for predicting the severity of diabetes mellitus (DM) and several cardiovascular diseases. However, whether HbA1c could predict the severity and clinical outcomes in patients with stable coronary artery disease (CAD) remains largely unknown. We determine relationship of HbA1c with severity and outcome in patients with stable CAD. Methods We enrolled 1433 patients with stable angina who underwent coronary angiography and were followed up for an average 12 months. The patients were classified into three groups by tertiles of baseline HbA1c level (low group <5.7%, n = 483; intermediate group 5.7 - 6.3%, n = 512; high group >6.3%, n = 438). The relationships between the plasma HbA1c and severity of CAD and early clinical outcomes were evaluated. Results High HbA1c was associated with three-vessel disease. Area under the receivers operating characteristic curve (AUC = 0.67, 95% CI: 0.63-0.71, P < 0.001) and multivariate logistic regression analysis suggested that HbA1C was an independent predictor of severity of CAD (OR = 1.60, 95% CI: 1.29-1.99, P < 0.001) even after adjusting for gender, age, risk factor of CAD, lipid profile and fasting blood glucose. During follow-up, 133 patients underwent prespecified outcomes. After adjusting for multiple variables in the Cox regression model, HbA1C remained to be an independent predictor of poor prognosis (HR = 1.28, 95%CI: 1.12- 1.45, P < 0.001). Conclusions We concluded that high level of baseline HbA1c appeared to be an independent predictor for the severity of CAD and poor outcome in patients with stable CAD. [ABSTRACT FROM AUTHOR]

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 <1.2 mmol/L, n = 103; High group ⩾1.2 mmol/L, n = 226). The relationship between the TG levels and early outcomes were evaluated. Results High TG group showed severer lipid profile and elevated inflammatory markers. During an average of 12-month follow-up, 47 out of 329 patients suffered from pre-specified outcomes. Area under the receivers operating characteristic curve suggested that TG, similar to serum Hemoglobin A1C (HbA1C), was a significant predictor of early outcome for diabetic patients with SAP (P = 0.002). In Cox regression models, after adjusted age, gender, body mass index, other lipid parameters, fasting blood glucose, high sensitivity C-reactive protein, neutrophil count and HbA1C, TG remained as an independent predictor of adverse prognosis. Conclusions High level of fasting TG (⩾1.2 mmol/L) was an independent predictor for early outcome of diabetic patients with SAP as like as HBA1c and number of affected coronary arteries in the era of revascularization and statin therapeutics. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]