Correlation Study Between Plasma Level of Pro-protein Convertase Subtilisin Kexin Type 9 and Coronary Artery Calcification / 中国循环杂志

Objective: To investigate the relationship between plasma level of pro-protein convertase subtilisin kexin type9 (PCSK9) and coronary artery calcification (CAC). Methods: A total of 380 consecutive chest pain patients without lipid-lowering therapy were enrolled. All patients received CT scan and coronary artery calcification (CAC) score measurement and were divided into 2 groups: CAC group, n=156 patients with CAC score>0 and Non-CAC group, n=224 patients with CAC score=0. CAC group was further classified in 3 subgroups as CAC score (1-100) subgroup, n=53, CAC score (101-400) subgroup, n=64 and CAC score>400 subgroup, n=39. Clinical data was collected, plasma levels of PCSK9 were measured in all patients and the relationship between PCSK9 and CAC score was investigated. Results: Plasma PCSK9 level in CAC group was higher than Non-CAC group (260.23±69.34) ng/ml vs (205.46±53.21) ng/ml, P<0.001; alone with CAC score increasing, PCSK9 level was elevating accordingly as in CAC score (1-100) subgroup, CAC score (101-400) subgroup and CAC score>400 subgroup, PCSK9 levels were (247.38±72.68) ng/ml, (264.87±57.63) ng/ml and (295.33±69.06) ng/ml respectively, all P<0.05. With adjusted traditional cardiovascular risk factors, multivariate regression analysis confirmed that plasma PCSK9 level was independently related to CAC score (β=0.584, P=0.002). In addition, the optimal cut-off value for PCSK9 predicting CAC was 228.58 ng/ml with sensitivity at 67% and specificity at 71%. Conclusion: Plasma PCSK9 level was related to CAC in chest pain patients without lipid-lowering therapy.

Impact of Smoking Status on Lipoprotein Subfractions: Data from an Untreated Chinese Cohort / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Cigarette smoking is one of the established risk factors of atherosclerotic cardiovascular disease, however, its impact on lipids is not completely understood, especially in the Chinese population. Therefore, this study evaluated the impact of smoking status (non, former, and current smoking) on the distribution of lipoprotein subfractions in untreated patients with angina-like chest pain.</p><p><b>METHODS</b>A total of 877 patients were consecutively enrolled and divided into nonsmoking (n = 518), former smoking (n = 103), and current smoking (n = 256) groups. Both low- and high-density lipoprotein cholesterol (LDL-C and HDL-C) subfractions were measured using the Quantimetrix Lipoprint System. The distributions of lipoprotein subfractions were evaluated among the groups.</p><p><b>RESULTS</b>Compared with nonsmoking subjects, the current smoking group had significantly lower large/medium HDL-C (both P < 0.001) concentration and large HDL subfraction percentage but higher small HDL-C and medium LDL-C concentrations as well as medium LDL subfraction percentage. Importantly, former smoking subjects showed elevated levels of large HDL-C concentration, large HDL particle percentage, and mean LDL particle size and attenuation in small HDL/LDL percentages and small LDL-C concentration, but these levels did not reach the optimal status compared with those of the non-smoking group (data not shown).</p><p><b>CONCLUSION</b>Smoking has an adverse impact on the lipoprotein subfractions, presented as lower large HDL particles besides higher small HDL and medium LDL particles, whereas smoking cessation could reverse these change to a certain degree.</p>

Short- and long-term effects of xuezhikang, an extract of cholestin, on serum proprotein convertase subtilisin/kexin type 9 levels / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the short- and long-term effects of Xuezhikang (XZK), an extract of cholestin, on proprotein convertase subtilisin/kexin type 9 (PCSK9) level.</p><p><b>METHODS</b>Thirty rats were randomly divided into three groups and were given saline, XZK 1,200 mg/kg or lovastatin 10 mg/kg respectively by daily gavage for 3 days (n=10 for each). Sixteen patients without previous lipid-lowering drug treatment for dyslipidemia received XZK 1,200 mg daily for 8 weeks. Fasting blood samples and liver tissue were collected at day 3 for rats, while the blood samples were obtained at baseline and week 8 from patients. The serum PCSK9 and lipid profile were measured. The expression of hepatic low density lipoprotein (LDL) receptor and sterol regulatory element binding protein 2 (SREBP-2) were measured by real time-PCR.</p><p><b>RESULTS</b>PCSK9 levels in rats were significantly increased in the XZK and lovastatin groups (P=0.002, P=0.003 vs. control) at day 3, while no significant differences were found in the levels of lipid parameters. PCSK9 levels in patients increased by 34% (P=0.006 vs. baseline) accompanied by total cholesterol and LDL-cholesterol decreased by 22% and 28% P=0.001, P=0.002 vs. baseline). The hepatic mRNA levels of LDL-receptor and SREBP-2 were significantly increased in the XZK and lovastatin groups.</p><p><b>CONCLUSION</b>XZK has significant impact on PCSK9 in a short- and long-term manner in both rats and humans. Moreover, the data indicated that as lovastatin, XZK increased PCSK9 levels through SREBP-2 pathway.</p>

Effects of Hedan Tablet () on lipid profile, proprotein convertase subtilisin/kexin type 9 and high-density lipoprotein subfractions in patients with hyperlipidemia: A primary study / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Hedan Tablet () on serum lipid profile, proprotein convertase subtilisin/kexin type 9 (PSCK9) and high-density lipoprotein (HDL) subfractions in patients with hyperlipidemia.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Kruppel-like factor 2 might mediate the rapamycin-induced arterial thrombosis in vivo: implications for stent thrombosis in patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Stent thrombosis is one of severe complications after sirolimus-eluting stent implantation. Rapamycin (sirolimus) promotes arterial thrombosis in in vivo studies. However, the underlying molecular and transcriptional mechanisms of this adverse effect have not been thoroughly investigated. This study was designed to examine the effects of rapamycin on the expression of the gene, Kruppel-like factor 2 (KLF2), and its transcriptional targets in mice.</p><p><b>METHODS</b>Mice were randomly divided into four groups: the control group (intraperitoneal injection with 2.5% of dimethyl sulfoxide (DMSO) only), rapamycin group (intraperitoneal injection with 2 mg/kg of rapamycin only), Ad-LacZ + rapamycin group (carotid arterial incubation with Ad-LacZ plus intraperitoneal injection with 2 mg/kg of rapamycin 10 days later), and Ad-KLF2 + rapamycin group (carotid arterial incubation with Ad-KLF2 plus intraperitoneal injection with 2 mg/kg rapamycin 10 days later). The carotid arterial thrombosis formation was induced by FeCl3 and the time of arterial thrombosis was determined. Finally, the RNA and protein of carotid arteries were extracted for KLF2, tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1), endothelial nitric oxide synthase (eNOS), thrombomodulin (TM) mRNA and protein analysis.</p><p><b>RESULTS</b>Compared with controls, treatment with rapamycin inhibited KLF2, eNOS and TM mRNA and protein expression, and enhanced TF and PAI-1 mRNA and protein expression, and shortened time to thrombotic occlusion from (1282 ± 347) seconds to (715 ± 120) seconds (P < 0.01) in vivo. Overexpression of KLF2 strongly reversed rapamycin-induced effects on KLF2, eNOS, TM, TF and PAI-1 expression. KLF2 overexpression increased the time to thrombotic occlusion to control levels in vivo.</p><p><b>CONCLUSIONS</b>Rapamycin induced an inhibition of KLF2 expression and an imbalance of anti- and pro-thrombotic gene expression, which promoted arterial thrombosis in vivo. Overexpression of KLF2 increased KLF2 expression and reversed time to thrombosis in vivo.</p>

Correlation of red cell distribution width with the severity of coronary artery disease: a large Chinese cohort study from a single center / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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, P < 0.001). 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, P < 0.05) and for a higher Gensini score (> 13, OR = 2.23, 95%CI: 1.62 - 3.08, P < 0.001). 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%.</p><p><b>CONCLUSION</b>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.</p>

miRNA changes in the reverse remodeling heart of rats / 中华心血管病杂志

<p><b>OBJECTIVE</b>To establish a reverse remodeling heart model in rats and observe collagen and TGF-β expression and relevant microRNAs changes during reverse remodeling.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>

Lovastatin protects mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis through activation of PI3K/Akt and ERK1/2 signaling pathways / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigated the effect of lovastatin on hypoxia and serum deprivation (Hypoxia/SD) induced rat MSCs apoptosis in vitro and associated signaling pathway changes.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>