The efficacy of Yiqi Huoxue method in treating coronary artery disease after percutaneous coronary intervention: A meta-analysis in accordance with PRISMA guideline.

BACKGROUND: Percutaneous coronary intervention (PCI), the most common method in treating coronary artery disease (CAD), has a variety of side effects. Yiqi Huoxue therapy (YQHX) can effectively alleviate the symptoms of patients and reduce the side effects. However, a reliable and systematic assessment of the methodologies is not available. METHODS: Seven electronic databases were searched to identify randomized controlled trials of YQHX method for CAD after PCI. The quality assessment of the trials included was performed by employing the Cochrane Risk of Bias tool. RESULTS: One thousand eight hundred sixty-eight patients from 23 randomized controlled trials were included in this review. The aggregated results showed that the experimental group got better effect in increasing ORR, TCMSRR, ECG, HDL-C, and in lowering the level of CRP, TC, and MACE in comparison with the control group. CONCLUSION: YQHX method is a valid complementary and alternative therapy in the management of CAD after PCI, and is an effective and safe therapy for CAD.

The efficacy of Yiqi Huoxue therapy for chronic heart failure: A meta-analysis in accordance with PRISMA guideline.

BACKGROUND: Chronic heart failure (CHF) is the final destination of most cardiovascular diseases and the most important cause of death. The main clinical manifestations were pulmonary congestion and decreased cardiac output. The purpose of this systematic review is to evaluate the effectiveness of Yiqi Huoxue therapy on CHF. METHODS: Seven electronic databases were searched to identify randomized controlled trials of Yiqi Huoxue (YQHX) method for CHF until April 30, 2020. The quality assessment of the included trials was performed by employing the Cochrane Risk of Bias tool and Jadad scale. RESULTS: Nineteen randomized controlled trials were included in our review. Most of the included trials were considered as low quality. The aggregated results suggested that experimental group with YQHX therapy got better effect in increasing overall response rate (risk ratio, RR = 1.21, 95% confidence interval, CI 1.15-1.27), traditional Chinese medicine (TCM) syndrome response rate (RR = 1.26, 95% CI 1.17-1.36), 6-minute walk test (RR = 2.14, 95% CI 1.05-3.22), left ventricular ejection fraction (RR = 0.97, 95% CI 0.60-1.34), and stroke volume (standardized mean difference, SMD = 0.94, 95% CI 0.23-1.56), and in lowering down the TCM syndrome scores (SMD = -0.78, 95% CI -0.91 to -0.64), Minnesota Living with Heart Failure questionnaire (SMD = -1.01, 95% CI -1.56 to -0.45), 6-month readmission rate (RR = 0.50, 95% CI 0.28-0.89), B-type natriuretic peptide (SMD = -0.89, 95% CI -1.52 to -0.25), NT-proBNP (SMD = -2.07, 95% CI -3.34 to -0.08), and C-reactive protein (SMD = -2.04, 95% CI -4.12 to -0.67) as compared to using conventional Western medicine alone. There were no significant differences found in left ventricular end diastolic diameter and E/E' between experimental groups and control groups. Moreover, the included sample capacity is small and the trails are all in Chinese. Quality of the evidence for outcomes were "low" and "very low" according to the GRADE assessment. CONCLUSION: YQHX is a valid complementary and alternative therapy in the management of CHF, especially in improving overall response rate, TCM syndrome response rate, 6-minute walk test, left ventricular ejection fraction, and stroke volume and in decreasing TCM syndrome scores, Minnesota Living with Heart Failure questionnaire, 6-month readmission rate, B-type natriuretic peptide, NT-proBNP, and C-reactive protein levels. Hence, YQHX is a relatively effective and safe therapy for CHF patients, which can be popularized and applied in the clinic. More long-term follow-up studies are still needed to substantiate and confirm the current findings.

Apolipoprotein E*Ɛ2 carriers exhibit high aspirin-treated platelet reactivity and low cardiovascular risk during long-term aspirin treatment.

OBJECTIVE: Apolipoprotein E (APOE) loci, including rs429358 (Ɛ4) and rs7412 (Ɛ2), are involved in cardiovascular (CV) health. However, their effect on the CV-protective effect of aspirin remains unknown. METHODS: A total of 515 aspirin-treated individuals with existing CV diseases were recruited, and their APOE genotypes, platelet functions and other routine laboratory parameters were assessed when they enrolled. The first major CV events (myocardial infarction, stroke, revascularisation and CV death) and all CV events (major CV events plus unstable angina and transient ischaemic attack) during a mean 5.2-year follow-up period were recorded. RESULTS: After adjusting for age, gender, BMI, lifestyle, lipid profiles and other CV drugs and comorbidities, Ɛ2 carriers were found to exhibit ~80% lower risk of major CV and 60% lower risk of all CV (HR = 0.186, CI: 0.048-0.715, P = 0.014; HR = 0.435, CI: 0.234-0.812, P = 0.009, respectively) than Ɛ2 noncarriers. Furthermore, high incidence of high platelet reactivity assessed by arachidonic acid-induced light transmission aggregometry (23.4 vs. 13.7%, P = 0.038), triglyceride and haemoglobin and low low-density lipoprotein were observed. Ɛ4 carriers had slightly increased cholesterol and hypercholesterolemia incidence relative to Ɛ4 noncarriers. CONCLUSIONS: Our results demonstrated that APOE*Ɛ2 carriers can derive additional CV benefit from long-term aspirin treatment. Moreover, it was observed that APOE2 interacts with cyclooxygenase-1 (COX-1) and upregulates its activity. The CV-protective effect of aspirin in Ɛ2 carriers is likely attributed to APOE2 upregulating vascular COX-1-mediated CV protective pathway, together with aspirin partially inhibiting platelet COX-1-mediated platelet aggregation.

Chronic Application of Low-Dose Aspirin Affects Multiple Parameters of Three Blood Cellular Types and Antithrombin Activity: A 1:1:1 Propensity Score Matching Analysis.

ABSTRACT: The mechanisms of aspirin antithrombotic actions have not been fully elucidated. We re-analyzed the data from the project Aspirin Resistance in Patients with Ischemic Atherothrombotic Diseases from April 2008 to June 2010. A total of 530 subjects were classified into 3 groups, including 40 patients without aspirin use, 24 patients taking 25-50 mg/d aspirin, and 466 patients taking 75-100 mg/d aspirin over 1 month. By 1:1:1 propensity score matching adjusting 15 primary clinical covariates, 51 patients (n = 17 per group) comprised the final sample. Hemostasis-related parameters and high platelet reactivity as measured by arachidonic acid-induced and adenosine diphosphate-induced light transmission aggregometry were compared in the 3 groups. A dose-dependent relationship was observed between aspirin and decreased high platelet reactivity incidence (PAA < 0.001, PADP < 0.01, respectively), decreased monocyte ratio (P = 0.052), increased antithrombin activity (P < 0.001), and increased platelet distribution width (P < 0.05). Aspirin at 25-50 mg/d is related to the lowest red blood cell (RBC) count, whereas 75-100 mg/d aspirin showed the highest RBC count among the 3 groups (4.52 ± 0.35 × 1012/L vs. 4.35 ± 0.57 × 1012/L vs. 4.80 ± 0.59 × 1012/L, P = 0.046). Our finding demonstrated that aspirin exerts its antithrombotic effects at least by antiplatelet function, enhancing antithrombin activity and suppressing monocytes in vivo. In addition, 3 blood cell types, namely RBCs, monocytes, and platelets, are involved in the aspirin antithrombotic mechanism. The cellular response to aspirin partially enhances the antithrombotic effects while partially inhibiting the effects.

A Protective Role of Paeoniflorin in Fluctuant Hyperglycemia-Induced Vascular Endothelial Injuries through Antioxidative and Anti-Inflammatory Effects and Reduction of PKCß1.

Hyperglycemia fluctuation is associated with diabetes mellitus (DM) complications when compared to persistent hyperglycemia. Previous studies have shown that paeoniflorin (PF), through its antiapoptosis, anti-inflammation, and antithrombotic properties, effectively protects against cardiovascular and cerebrovascular disease. However, the mechanism underlying the protection from PF against vascular injuries induced by hyperglycemia fluctuations remains poorly understood. Herein, we investigated the potential protective role of PF on human umbilical vein endothelial cells (HUVECs) subjected to intermittent glucose levels in vitro and in DM rats with fluctuating hyperglycemia in vivo. A remarkable increased apoptosis associated with elevated inflammation, increased oxidative stress, and high protein level of PKCß1 was induced in HUVECs by intermittently changing glucose for 8 days, and PF recovered those detrimental changes. LY333531, a potent PKCß1 inhibitor, and metformin manifested similar effects. Additionally, in DM rats with fluctuating hyperglycemia, PF protected against vascular damage as what has been observed in vitro. Taken together, PF attenuates the vascular injury induced by fluctuant hyperglycemia through oxidative stress inhibition, inflammatory reaction reduction, and PKCß1 protein level repression, suggesting its perspective clinical usage.

Effect of tetramethylpyrazine and hyperlipidemia on hepcidin homeostasis in mice.

Iron homeostasis is strictly regulated in mammals, and disordered iron metabolism is recognized as a risk factor for various diseases, including cardiovascular disease. The hepcidin­ferroportin axis is the key signaling mechanism that controls systemic iron homeostasis. Increased serum hepcidin is associated with multiple types of cancer and atherosclerosis (AS), and therapeutics that decrease hepcidin levels have been proposed to treat these diseases. However, the effects of abnormal circulating hepcidin on hyperlipidemia remain unexploited. The natural compound tetramethylpyrazine (TMP) has been reported to have therapeutic effects on cardiovascular diseases, whereas the mechanisms involved remain incompletely understood. Thus, the effects of TMP on the expression of hepcidin in hyperlipidemic mice were investigated and the mechanisms involved were explored. Hyperlipidemia increased serum hepcidin, which was inhibited by TMP intervention. The results also indicated that TMP may decrease hepcidin expression via inhibition of Stat3 signaling. These findings suggest a promising rationale to prevent and hyperlidemia by targeting hepcidin or its upstream regulators, and highlight the potential application of natural compounds in treating hepcidin disorder­associated diseases.

The Influence of Hyperlipidemia on Endothelial Function of FPN1 Tek-Cre Mice and the Intervention Effect of Tetramethylpyrazine.

BACKGROUND/AIMS: Systemic iron homeostasis is strictly governed in mammals; however, disordered iron metabolism (such as excess iron burden) is recognized as a risk factor for various types of diseases including AS (Atherosclerosis). The hepcidin-ferroportin axis plays the key role in regulation of iron homeostasis and modulation of this signaling could be a potential therapeutic strategy in the treatment of these diseases. TMP (Tetramethylpyrazine) has been reported to have therapeutical effect on AS. Here, we aimed to investigate the effect of iron overload under hyperlipidemia condition on the endothelial injury, inflammation and oxidative stress by employing FPN1 Tek-cre mouse model with or without TMP intervention. METHODS: Subjects for this study were 80 FPN1 Tek-cre mice and 40 C57BL/6 mice and we randomly divided them into six groups: Group N: C57BL/6 mice with normal diet, Group M: C57BL/6 mice with high-fat diet, Group FN: FPN1 Tek-cre mice with normal diet, Group FNT: FPN1 Tek-cre mice with normal diet and TMP injection, Group FM: FPN1 Tek-cre mice with high-fat diet, Group FMT: FPN1 Tek-cre mice with high-fat diet and TMP injection. After seven days of treatment, blood samples were obtained to detect the levels of blood lipids, Hepcidin, NO, ET-1, ROS, MDA, SOD, IL-1, IL-6 and TNF-α respectively. The liver and aorta were used for testing the lipid deposition by using hematoxylin and eosin(HE). RESULTS: Hyperlipidemia could cause iron overload in the aorta and increased serum hepcidin level, particularly in FPN1 Tek-cre mice, and can be reversed by TMP intervention. Knockout of Fpn1 induced increase of serum hepcidin, exacerbated endothelial dysfunction, oxidative stress and inflammatory response, particularly under hyperlipidemia condition. TMP intervention attenuated these processes. CONCLUSIONS: Our study signifies the potential application of certain natural compounds to ameliorating iron disorders induced by hyperlipidemia and protecting on endothelial function through modulation of hepcidin-ferroportin signaling.

[Correlation Research on Blood Glucose Fluctuation in Type 2 Diabetes Mellitus Patients and Vas- cular Endothelial Injury/Platelet Activation/PKCß1 Expression].

Objective To observe the correlation between blood glucose fluctuation in type 2 dia- betes mellitus ( T2DM) patients and vascular endothelial injury/platelet activation/protein kinase Cß1 (PKCpß1). Methods Capillary blood was collected from finger tips of 38 T2DM patients at 7 time points, i.e., before 3 meals, 2 h after 3 meals, 21:00 pm before sleep. The mean amplitude of plasma glucose excursions (MAGE) was calculated. The peripheral blood platelet aggregation rate (PAG) induced by a- denosine diphosphate (ADP) and platelet membrane protein level of CD62p were determined by platelet fluorescent aggregometer and flow cytometry respectively. HbAlc was measured by ion-exchange high- performance liquid chromatography. Serum levels of E-selectin, von Willebrand factor ( vWF), and PKCß1 were detected by ELISA. Meanwhile, liver and renal functions, blood lipids were also measured. Their blood pressure was measured and body mass index (BMI) calculated. By taking HbA1c as a moni- tored index for assessing long-term glucose control, MAGE as an indicator for assessing glucose fluctua- tion, the correlations between serum markers for vascular endothelial injury (levels of E-selectin and vWF)/platelet activation indices (PAG and CD62p expression) and PKCß1 level/MAGE respectively were analyzed using Pearson correlation analysis and multivariant Logistic regression. The correlations be- tween PKCß1 level and MAGE/HbA1 c were also analyzed. Results In simple correlation analysis, there were no significant correlations between age/BMI/course of disease/medical history/serum levels of E-se- lectin/vWF/PKCß1/PAG/CD62p expression and MAGE (P >0. 05). There were significant correlations be- tween vascular endothelial injury markers ( E-selectin and vWF)/platelet activation indicators ( PAG, CD62p expression) and MAGE (r =0. 468, 0. 609, 0. 451 , 0. 674; P <0. 01). There were significant corre- lations between PKCß1 and glucose assessment indicators (MAGE and HbA1c)/vascular endothelial inju- ry markers ( E-selectin and vWF) , platelet activation indicators ( PAG and CD62p expression) (r = 0. 643, 0. 705, 0. 394, 0. 665, 0. 441 , 0. 577; P <0. 01). Conclusion PKCß1 , the key regulatory gene of coronary artery disease with blood stasis syndrome, was closely related with the degree of vascular en- dothelial injury and aggregation level of platelet activation in T2DM patients with blood glucose fluctuation.

Anti-inflammatory effects of tanshinone IIA on atherosclerostic vessels of ovariectomized ApoE mice are mediated by estrogen receptor activation and through the ERK signaling pathway.

AIMS: Estrogen plays a protective role in atherosclerosis. Our preliminary work demonstrated that the active conformation of Tanshinone IIA(TanIIA) is similar to the 17ß-estradiol and it can bind to the estrogen receptor. Here, we hypothesized that Tanshinone IIA might have anti-inflammatory and anti-oxidative effects in atherosclerosis, mediated through estrogen receptor activation. METHODS: Subjects for this study were 120 apoE(-/-) female mice and 20 C57/BL female mice. The apoE(-/-) mice were ovariectomized (OVX) and the C57/BL mice were sham ovariectomized. The sham OVX mice were maintained on a normal diet (NOR) group. The OVX apoE(-/-) mice were fed a high fat diet and randomly divided into 6 groups: Model (MOD) group which was fed a high fat diet only, E2 group were given estrogen (E2) 0.13 mg/kg/d; E2+ICI group were given E2:0.13 mg/kg/d and ICI182780:65 mg/kg/m; TLD group (TanIIA low dose) were given TanIIA: 30 mg/kg/d; THD group (TanIIA high dose) were given TanIIA:60 mg/kg/d; and TLD+ICI group were given TanIIA 30 mg/kg/d and ICI182780 65 mg/kg/m. After three months of treatment, the aorta and the blood of the mice from each group was collected. The aorta were used for testing the lipid deposition by using hematoxylin and eosin(HE) and oil red O staining and for testing the expression of p-ERK1/2 by Western blot. The blood was used for testing the serum cholesterol, superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA), nuclear factor kappa (NF-κB), soluble intercellular cell adhesion molecule-1 (sICAM-1), activating protein-1 (AP-1), E-selectin and 17ß-estradiol in serum. RESULTS: Tanshinone IIA significantly reduced the lipid deposition in aorta, decreased the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), very low density lipoprotein (VLDL), MDA, NF-κB, sICAM-1, AP-1, and E-selectin in serum but increased the levels of high density lipoprotein (HDL) and SOD in serum. Tanshinone IIA also suppressed the expression of p-ERK1/2. Tanshinone IIA had no effect of level of serum 17ß-estradiol levels. All of the effects of Tanshinone IIA were similar to estrogen and were inhibited by the estrogen receptor antagonist ICI182780. CONCLUSION: Tanshinone IIA may play an anti-inflammatory and anti-oxidative stress role in OVX atherosclerotic apoE(-/-) mice by activating the estrogen receptor through the ERK signaling pathway. Therefore, Tanshinone IIA, as a phytoestrogen, could be used for estrogen replacement therapy for cardiovascular disease of postmenopausal women.

[Effect of Chinese herbal drug-containing serum for activating blood, activating blood and dispelling toxin on TNF-alpha-induced adherence between endothelial cells and neutrophils and the expression of MAPK pathway].

OBJECTIVE: To explore the effect of drug-containing serum of Chinese herbal compounds [Xiongshao Capsule (XS, for activating blood) and Huanglian Capsule (HL, for dispelling toxin)] on tumor necrosis factor-alpha (TNF-alpha)-induced adherence between human umbilical vein endothelial cells (HUVECs) and polymorphonuclear neutrophils (PMN), inflammatory reaction and expression of related proteins in mitogen-activated protein kinase (MAPK) pathway. METHODS: Thirty-two rats were randomly divided into four groups (8 in each group) using random digit table: the blank control group treated with distilled water, the test group I treated with Chinese herbal compound of XS (0.135 g/kg), the test group II treated with Chinese herbal compound of HL (0.135 g/kg), and the test group Ill treated with Chinese herbal compound of XS (0.135 g/kg) and HL (0.135 g/kg). All medication was given by gastrogavage once a day for a week. Rats' blood serum was harvested 1 h after the last administration to prepare drug-containing serum. HUVECs were exposed to TNF-alpha (100 ng/mL) to induce cell injury model and incubated with corresponding drug-containing serum (10%) for 24 h. Normal rats' serum was given to cells in the blank control group and the model group, while XC + HL containing serum was given to cells in the rest 3 groups. The adherence of HUVECs and PMN cells was detected by using rose bengal strain. Levels of E-selectin, intercellular adhesion molecule-1 (ICAM-1), and interleukin-1beta (IL-1P) in the supernatant of cultured HU-VECs were determined by ELISA. Protein expressions of mitogen-activated protein kinases p38 (p38MAPK) and extracellular signal-regulated kinase 1/2 (ERK 12) were determined by Western blot. RESULTS: Compared with the blank control group, HUVECs were seriously injured; PMN adherence amount significantly increased; levels of E-selectin, ICAM-1, and IL-1beta increased; expression levels of p-p38MAPK and p-ERK 1/2 in the supernatant of HUVECs significantly increased in the model group (all P < 0.01). Compared with the model group, HUVECs-PMN adherence amount decreased (P < 0.05); levels of E-selectin, ICAM-1, and IL-1 beta in the supernatant of HUVECs decreased (P < 0.01, P < 0.05); expression levels of p-p38MAPK and p-ERK 1/2 of endothelial cells decreased in the test group I, II, and III (P < 0.01). CONCLUSIONS: Drug-containing serums of activating blood, activating blood and dispelling toxin could attenuate TNF-alpha induced injury of HUVECs, inhibit HUVECs-PMN adherence and the release of adhesion factors. Its mechanism might be involved with protein phosphorylation of p38MAPK and ERK 1/2 in the MAPK pathway.

Effective components of Panax quinquefolius and Corydalis tuber protect the myocardium by inhibiting platelet activation and improving the hypercoagulable state.

The aim of the present study was to investigate the effects of extract of Panax quinquefolius and Corydalis tuber (EPC) on platelet activation and the hypercoagulable state in rats with acute myocardial infarction (AMI). The MI model in Wistar rats was induced by coronary artery ligation. Sham surgery was performed as a control. The surviving rats that underwent MI surgery were divided into control (administered normal saline), metoprolol (9 mg/kg) and low-, moderate- and high-dose EPC groups (0.54, 1.08 g/kg and 2.16 g/kg, respectively). Saline, metoprolol and EPC were administered by gastrogavage for two consecutive weeks. The morphological changes of the myocardium were assessed by hematoxylin and eosin and nitroblue tetrazolium staining. Serum von Willebrand factor (vWF), D-dimer (DD), platelet membrane glycoproteins IIb-IIIa (GPIIb-IIIa) and CD62P levels were assessed using enzyme-linked immunosorbent assay. EPC attenuated the pathological changes of the myocardium. High-dose EPC decreased the serum concentration of vWF when compared with control group. Moderate and high doses of EPC decreased the DD and GPIIb-IIIa levels, and the CD62P level was gradually decreased with EPC dose escalation. The results therefore demonstrated that EPC protects the myocardium by inhibiting platelet activation and improving the hypercoagulable state in a rat model of AMI.

Protective effect of propyl gallate against oxidized low-density lipoprotein-induced injury of endothelial cells.

OBJECTIVE: To evaluate the protective effect of propyl gallate (PG), an alkyl ester of gallic acid which is an active ingredient of Radix Paeoniae, against oxidized low-density lipoprotein (ox-LDL)-induced apoptosis and death in endothelial cells (ECs) and to find out its preliminary mechanism. METHODS: The cultured endothelial cells were divided into normal, model (ox-LDL), control (fetal bovine serum), PG high dose (20 µg/mL), PG middle dose (10 µg/mL), and PG low dose (5 µg/mL) groups, each derived from three different pools of umbilical cords. The model of injured human umbilical vein endothelial cells (HUVECs) was induced by ox-LDL. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, Hoechst 33258 staining, flow cytometry and measurement of nitrogen monoxidum (NO) release were used to evaluate the protective effect of PG against ox-LDL-induced apoptosis and death in HUVECs. To find out the mechanism of this protective effect, the expression of endothelial nitric oxide synthase (eNOS) mRNA, eNOS protein expression, immunofluorescence of intracellular reactive oxygen species (ROS) and activities of malondialdehyde (MDA), superoxidedismutase (SOD) and glutathione peroxidase (GPx) were observed. RESULTS: PG significantly reduced ox-LDL-induced apoptosis and cell death. The percentage of cells death and apoptosis was significantly higher in the ox-LDL group than that in the control group (P<0.05). Compared with the control group, the cells death and apoptosis of PG group was no different (P>0.05). As compared with the ox-LDL group, results of the PG high dose group showed that cell viability was significantly increased (P<0.05), the level of NO release, expression of eNOS mRNA, densitometric value of eNOS protein expression, as well as the activities of SOD and GPx were all significantly higher (all P<0.05). CONCLUSION: PG could potentially serve as a novel endothelial protective agent against ox-LDL-induced injury of endothelial cell.

Effects of Panax quinquefolium saponin on phosphatidylinositol 3-kinase/serine threonine kinase pathway of neonatal rat myocardial cells subjected to hypoxia.

OBJECTIVE: To explore the effects of Panax Quinquefolium Saponin (PQS) on phosphatidylinositol 3-kinase/serine threonine kinase (PI3K/Akt) pathway of neonatal rat myocardial cells subjected to hypoxia. METHODS: Neonatal rat myocardial cells were cultured in vitro. After the myocardial cell injury was induced by hypoxia, the cells were randomized into 5 groups: the normal group, the model group, the positive control group (Ciclosporin A, 2 µ mol/L), the low-dose PQS group (PQSL, 25mg/L), and the high-dose PQS group (PQSH, 50 mg/L). Morphology and behavior of myocardial cells were observed under an inverted microscope. Apoptosis rate and lactate dehydrogenase (LDH) leakage rate of myocardial cells were determined by colorimetry. Mitochondrial transmembrane potential was assessed using a fluorexon laser. Phospho-glycogen synthase kinase (GSK)-3ß and phospho-Akt as well as cytochrome C were determined by Western blot RESULTS: LDH leakage in the Ciclosporin A group, PQSH group and PQSL group reduced progressively compared with the model group (P<0.05). Akt and GSK-3ß was strongly phosphorylated after treatment with Ciclosporin A and PQS compared with the model group (P<0.05, P<0.01). Compared with the model group (16.41±1.74; 35.28±6.30), both the integrated optical density of mitochondrial permeability transition pore (MPTP) and the mitochondrial transmembrane potential significantly increased in the PQSH group (42.74±2.12; 71.36±6.54) and the PQSL group (39.58±1.49; 66.99±5.45; P<0.05, P<0.01). However, the protein of cytochrome C outside the mitochondrion decreased in the PQSH group (273.66±14.61) and the PQSL group (259.62±17.31) compared with the model group (502.41±17.76; P<0.05). CONCLUSION: Through activation of the PI3K/Akt pathway and inhibition of the MPTP, PQS might protect the heart against ischemia injury and apoptosis of myocardial cells.

[The estrogen-like protective effect of ginsenoside Rb3 on oxidative stress and dysfunction of endothelial cells induced by oxidized low-density lipoprotein].

Ginsenoside Rb3 (GRb3) is one of the main components in plasma of Panax quinquefolius Saponin of stem and leaf (PQS), which can be into human plasma. Previous studies have found PQS has estrogen-like vascular protective effects. In the present study, we investigated the estrogen-like protective effect of GRb3 on oxidative stress and dysfunction of endothelial cells induced by oxidized low-density lipoprotein. The activities of SOD, NOS and the contents of MDA in the cell lysate were examined by enzyme method or spectrophotometry. The NO and ET-1 concentrations in the cell culture supernatant were measured by ELISA method. The iNOS and eNOS mRNA expression were measured by real time RT-PCR, while the phosphorylation levels of Akt was measured by Western blotting. The results showed that GRb3 could enhance the activity of SOD, reduce the content of MDA, increase the level of NOS, NO, ET-1 and iNOS mRNA expression while decrease the eNOS mRNA expression and the phosphorylation level of Akt. These effects were blocked by estrogen receptor antagonist ICI182780. GRb3 can play a role in protecting vascular endothelial cells by estrogen receptors, the protective mechanism is similar to 17-ß estrodiol.

[Effect of activating blood circulation or activating blood circulation and detoxication on platelet activation, inflammation, and coagulation status in acute myocardial infarction rats].

OBJECTIVE: To observe the effect of activating blood circulation drugs or activating blood circulation and detoxication drugs on indices of platelet activation, inflammation, and coagulation status correlated with blood-stasis and toxin in acute myocardial infarction rats. METHODS: Totally 100 male SD rats were randomly divided into the sham-operation group, the model group, the activating blood circulation group, the activating blood circulation and detoxication group, and the metoprolol group, 20 in each group. Rats in the activating blood circulation group were administered with Xiongshao Capsule at the daily dose of 0.39 g/kg. Rats in the activating blood circulation and detoxication group were administered with Xiongshao Capsule (at the daily dose of 0.39 g/kg) and Huanglian Capsule (at the daily dose of 0.135 g/kg). Rats in the metoprolol group received metoprolol at the daily dose of 2.25 mg/kg. And rats in the rest two groups were administered with normal saline. All medication lasted for 3 successive weeks. After the last administration, the rat model of acute myocardial infarction was prepared by ligation of left anterior descending artery. No ligation was given to rats in the sham-operation group. Animals were sacrificed 24 h after modeling. Tumor necrosis factor-α (TNF-α), ß-thromboglobulin (ß-TG), platelet α granule membrane protein-140 (GMP-140), 11 dehydro-thromboxane B2 (11-DH-TXB2), fibrinopeptide A (FPA), antithrombin III (AT-III), and D-dimer (DD) were detected by ELISA. The mRNA expression of TNF-α was tested by RT-PCR. RESULTS: Platelet activation parameters were significantly increased in the model group, when compared with the sham-operation group (P < 0.01). Compared with the model group, all indices (except GMP-140 in the metoprolol group) obviously decreased in each medicated group (P < 0.01, P < 0.05). Besides, ß-TG and 11-DH-TXB2 were superior in the activating blood circulation and detoxication group to that of the metoprolol group (P < 0.05). But 11-DH-TXB2 was also obviously superior in the activating blood circulation and detoxication group to that of the activating blood circulation group (P < 0.05). Compared with the sham-operation group, an obviously hypercoagulable state was obviously shown in the AMI model group, with significantly increased FPA and DD (P < 0.05 or 0.01) and significantly decreased AT III (P < 0.01). Compared with the model group, the FPA level significantly decreased in each medicated group (P < 0.01), and the AT III level significantly increased in the activating blood circulation group and the activating blood circulation and detoxication group (both P < 0.01). The level of DD obviously decreased in the activating blood circulation and detoxication group (P < 0.01). Besides, the 3 indices were superior in the activating blood circulation and detoxication group to those of the metoprolol group (P < 0.05). Compared with the sham-operation group, the serum TNF-α level and myocardial TNF-α mRNA expression were significantly increased in the model group (P < 0.05, P < 0.01). Compared with the model group, not only the serum TNF-α level was significantly decreased, but also the TNF-α gene expression in the myocardial tissue was improved in the activating blood circulation and detoxication group (P < 0.01). CONCLUSION: Combined use of activating blood circulation and detoxication drugs could play an effective role in treatment of coronary heart disease by fighting against platelet activation, improving the hypercoagulable state, and inhibiting inflammation, which was significantly better than using activating blood circulation and removing stasis drugs alone.

The Expression of CD14(+)CD16(+) Monocyte Subpopulation in Coronary Heart Disease Patients with Blood Stasis Syndrome.

Blood stasis syndrome (BSS), a comprehensive pathological state, is one of the traditional Chinese medicine syndromes of coronary heart disease (CHD). In our previous study, we investigated that Fc γ RIIIA (also called CD14(+)CD16(+) monocyte subpopulation) is one of the differentially expressed genes related to CHD patients and its possible role in the atherosclerotic formation and plaque rupture. However, whether or not the deregulation of CD14(+)CD16(+) monocyte subpopulation expression is implicated in the pathogenesis of CHD patients with BSS has not yet been elucidated. In this study, we found that there was no significant difference between CHD patients with BSS and non-BSS in CD14(+)CD16(+) monocyte subpopulation at gene level. Moreover, the protein level of CD14(+)CD16(+) monocyte subpopulation in CHD patients with BSS was increased significantly when compared to the CHD patients with non-BSS. Additionally, the level of inflammatory cytokines downstream of CD14(+)CD16(+) monocyte subpopulation such as TNF- α and IL-1 in sera was much higher in CHD patients with BSS than that in CHD patients with non-BSS. Taken together, these results indicated that CD14(+)CD16(+) monocyte subpopulation was implicated in the pathogenesis of CHD patients with BSS, which may be one of the bases of the essence of BSS investigation.

[Characteristics and related risk factors of arterial elasticity in prehypertensive persons].

OBJECTIVE: To explore the characteristics and related risk factors of arterial elasticity in persons with prehypertension, high-normal blood lipid and(or) impaired glucose regulation(impaired fasting glucose and(or) impaired glucose tolerance). METHODS: After receiving physical and biochemical examinations, a total of 1238 persons were enrolled. Among them, the etiologies were prehypertension (n = 65), high-normal blood lipid (n = 156), impaired glucose regulation (n = 159), prehypertension and high-normal blood lipid (n = 85), prehypertension and impaired glucose regulation (n = 77), high-normal blood lipid and impaired glucose regulation (n = 55) and prehypertension, high-normal blood lipid and impaired glucose regulation (n = 9). Also 332 healthy subjects, 113 hypertensive patients, 150 hyperlipidemics and 37 diabetics were enrolled as controls. Systemic vascular compliance (SVC), systemic vascular resistance (SVR), brachial artery distensibility (BAD) were measured with Dynapulse 200 M (Pulse Metric, Inc., USA). RESULTS: In persons with prehypertension, SVC was lower than healty group ((1.14 ± 0.20) ml vs (1.26 ± 0.23) ml, P < 0.01)and higher than hypertensive group ((1.11 ± 0.18) ml, P = 0.011), SVR higher than healty group (157 ± 29) kPa×s×L(-1) vs (148 ± 25) kPa×s×L(-1), P = 0.012) and lower than hypertensive group ((166 ± 36) kPa×s×L(-1), P < 0.01)and BAD lower than healty group(5.93% ± 1.14% vs 6.50% ± 1.30%, P < 0.01). Among different groups with prehypertension, high-normal blood lipid and(or) impaired glucose regulation, SVC, SVR and BAD had significant differences. As indicated by multiple linear regression analysis, blood pressure was an independent risk factor of arterial elasticity. CONCLUSIONS: Vascular function becomes damaged in prehypertensive stage. As an independent risk factor, blood pressure had more potent effect than lipid and blood glucose. Multiple cardiovascular risk factors with high-normal value may affect vascular function more strongly.

Influence of high blood glucose fluctuation on endothelial function of type 2 diabetes mellitus rats and effects of Panax Quinquefolius Saponin of stem and leaf.

OBJECTIVE: To observe the influence of high blood glucose fluctuation on the endothelial function of type 2 diabetes mellitus (T2DM) rats and the effects of Panax Quinquefolius Saponin (PQS) of stem and leaf. METHODS: The T2DM model was induced by intraperitoneal injection of a small dose of streptozotocin (STZ, 35 mg/kg) plus high fat and high caloric laboratory chow. Then, diabetic rats were divided into steady high blood glucose (SHG) group and fluctuant high blood glucose (FHG) group according to fasting blood glucose coefficient of variation (FBG-CV), and then, the FHG group rats were divided into 4 groups according to the level of FBG-CV and fasting blood glucose: PQS 30 mg/(kg·d) group, PQS 60 mg/(kg·d) group, metformin hydrochloride control (MHC) group, and FHG control group, 10 in each group. Meanwhile, 10 rats without any treatment were used as normal control (NOR) group. Eight weeks later, the aortic arteries histology, plasma hepatocyte growth factor (HGF), and serum nitric oxide (NO), endothelin-1 (ET-1), tumor necrosis factor α (TNF-α), and soluble intercellular adhesion molecule 1 (sICAM-1) were measured. RESULTS: In comparison with the NOR group, the level of plasma HGF and serum NO, ET-1 and TNF-α, and sICAM-1 in SHG and FHG control groups were all significantly increased (P<0.01); in comparison with the SHG group, plasma HGF and serum NO, ET-1, TNF-α, and sICAM-1 in FHG group were all significantly increased further (P<0.01 or P<0.05); meanwhile, in comparison with the FHG control group, the level of plasma HGF and serum NO, ET-1, TNF-α, and sICAM-1 in PQS and MHC groups were all decreased significantly (P<0.01). However, comparison of the aortic arteries histology among groups showed no significant differences either before or after treatment. CONCLUSION: Blood glucose fluctuation could facilitate the development of vascular endothelial dysfunction in T2DM rats, while PQS could improve the endothelial function of T2DM rats with high blood glucose fluctuation, which may be related to its effects of relieving vessel stress, decreasing vasoconstrictor ET-1 production, preventing compensated increase of NO, and reducing inflammatory reaction.