Macrophage migration inhibitory factor promoter polymorphisms (-794 CATT5-8): Relationship with soluble MIF levels in coronary atherosclerotic disease subjects.

BACKGROUND: We analyzed the relationship of -794 CATT5-8 MIF polymorphisms with soluble MIF in Coronary Atherosclerotic Disease (CAD) patients. METHODS: A total of 256 patients selected, on which 186 normal-coronary and 70 Coronary artery disease subjects, were recruited in the study (Retrospectively registered). Genotyping of -794 CATT5-8 polymorphisms were performed by PCR and DNA sequencing. Serum MIF levels were measured using an ELISA kit. Patients were classified by coronary angiogram, and CAD based on Gensini's integral degree (angiographic scoring system). RESULTS: The allele frequency and genotype frequency of -794 CATT5-8 did not show any differences in normal-coronary subjects and CAD subjects. In CAD patients, serum MIF levels was lower in CATT (5) subjects than in CATT (7) subjects, while the genotype of -794 CATT5-8 did not show differences in serum MIF levels. In addition, we found a decrease in serum MIF levels in carriers of the (5/5) genotypes the -794 CATT5-8 MIF polymorphisms, although it was not significant. There was no relationship of CAD class and the allele frequency of -794 CATT5-8. CONCLUSIONS: This study found no association between CAD class and -794 CATT5-8 MIF polymorphisms with soluble MIF levels in CAD Subjects. TRIAL REGISTRATION: NCT01750502 (November 2012, Retrospectively registered).

Ablation of atrioventricular nodal reentrant tachycardia in a patient with reversal of slow and fast pathways inputs into the atrioventricular node.

We report a case of atrioventricular nodal reentrant tachycardia (AVNRT) coexistent with His bundle anomaly and atrial septal defects. The His-bundle potential was recorded at the coronary sinus (CS) ostium. Fractionated atrial potentials and an A:V electrogram ratio 1:3 were recorded at the anterior septum of the tricuspid annulus approximately 2 cm from CS ostium. Radiofrequency catheter ablation at the anterior septum of the tricuspid annulus effectively eliminated AVNRT.

[Impact of CACNA1C polymorphisms on antihypertensive efficacy of calcium channel blocker].

OBJECTIVE: To explore the relationship between genetic polymorphisms of CACNA1C that encoded the a1c subunit of the L-type calcium channel and the efficacy of calcium channel blocker (CCB, Nifedipine extended release tablet/20 mg/d) in essential hypertension (EH) patients of Han Chinese in Wenzhou. METHODS: For the enrolled 103 EH patients, Multiplex Polymerase Chain Reaction (Multi-PCR) and matrix assisted laser desorption ionization time of flight MS (MLDI-TOF MS) were performed to detect their genotypes (rs216008, rs1051375, rs2299661, rs10848683, rs215976), blood pressure (BP) after CCB monotherapy was compared among patients with different genotypes. RESULTS: (1) Blood pressure was significantly reduced in all patients post CCB (P < 0.05 vs. pre-CCB). (2) Diastolic blood pressure reduction was more significant in subjects with rs2299661 C/C genotype (wild genotype) than in subjects with rs2299661C/G and rs2299661G/G genotype (mutational genotype) [(12.46 ± 7.91) mm Hg (1 mm Hg = 0.133 kPa) vs. (7.22 ± 8.01) mm Hg and (5.93 ± 9.77) mm Hg, P < 0.05]. (3) Systolic blood pressure reduction was more significant in subjects with rs216008 C/C genotype (wild genotype) than in subjects with rs216008 C/T genotype (mutational genotype) [(20.60 ± 12.35) mm Hg vs. (13.62 ± 10.21) mm Hg, P < 0.05]. (4) Blood pressure reduction was similar between subjects with genotype of rs1051375, rs10848683 and rs215976. CONCLUSION: EH patients with wild genotype of rs2299661 and rs216008 in CACNA1C are more likely to be responders of CCB monotherapy.

[Effect of astragaloside against the oxidative damage on endothelial cells].

OBJECTIVE: To observe the effect of astragaloside on oxidative low-density lipoprotein (Ox-LDL) mediated oxidative damage of endothelial progenitor cells (EPCs). METHODS: Peripheral blood mononuclear cells(PBMCs) were isolated by Ficoll density gradient centrifugation, and EPCs were identified by flow cytometry. Adherent cells were collected after seven-day incubation and randomly divided into the normal control group, the Ox-LDL group (as the model group, at the dose of 100 microg/mL), the low, middle, and high astragaloside groups (with 100 microg/mL Ox-LDL plus 2, 10, and 50 microg/mL astragaloside). Twenty-four h later, the proliferation and adhesion capabilities of EPCs were observed using MTT colorimetry and the adhesion capability detection. Levels of superoxide dismutase (SOD) and malonaldehyde (MDA) in the cell supernate of each group were determined. RESULTS: After Ox-LDL damage, the proliferative and adhesive capacities of EPCs were significantly injured (53 +/- 8 vs 42 +/- 6, 0.49 +/- 0.12 vs 0.37 +/- 0.02, both P<0.05). The SOD content obviously decreased (21.95 +/- 1.43 vs 14.76 +/- 3.99, P<0.01), the MDA content obviously increased (3.72 +/- 0.30 vs 5.57 +/- 0.64, P<0.01). After intervened by astragaloside for 24 h, the proliferative and adhesive capacities of EPCs were significantly improved. The SOD contents of astragaloside intervention groups were obviously improved and the MDA content obviously lowered. CONCLUSIONS: Astragaloside showed significant protection on Ox-LDL damaged EPCs. Its mechanism might be correlated with antioxidative damage.

Potassium channels: possible new therapeutic targets in Parkinson's disease.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders and still remains incurable. New targets for potential pharmacological intervention should be explored and evaluated in order to slow down, delay or reverse the progress of this disease, and/or to avoid the serious side effects of levodopa praeparatum. Potassium (K+) channels widely express in basal ganglia and play crucial roles in the pathophysiology of PD, thereby raising their therapeutic application. Based on data from some pilot studies, we propose that K+ channels may provide possible new therapeutic targets for slowing down the progressive loss of dopamine neurons in PD. The most promising targets of K+ channels, including Kv, KATP, Kir, SK, and K2P channels, etc. deserve further pursuit for making comprehensive use of their novel therapeutic potential. Attempts to confirm this hypothesis may lead to new therapeutic strategy of PD.

Contrast-enhanced sonographic characteristics of neovascularization in carotid atherosclerotic plaques.

PURPOSE: To evaluate neovascularization within carotid atherosclerotic plaques with contrast-enhanced sonography. METHODS: We used contrast-enhanced sonography to examine 63 patients with carotid atherosclerotic plaques. The features of neovascularization within the plaques were analyzed and correlated with plaque size and echogenicity. RESULTS: There were 81 atherosclerotic plaques, 62 of which (43 soft and 19 mixed) enhanced after injection of a contrast agent. The enhancement occurred from the carotid wall to the center of the plaque with a short-line pattern in 36 plaques, whereas 26 plaques enhanced from both the carotid wall and the carotid lumen, with a sparse spot pattern. The arrival time of contrast was shorter (p < 0.001) and time to peak was longer (p < 0.001) in the plaques than in the carotid lumen. Time to peak was shorter, whereas enhanced intensity was greater in soft plaques than in mixed plaques (p < 0.01 and p < 0.05, respectively). Among the 19 unenhanced plaques, 6 were hard, 3 were calcified, 3 were soft, and 7 were mixed. The thickness of the unenhanced plaques was <2.4 mm. CONCLUSION: Contrast-enhanced sonography allows the noninvasive, dynamic evaluation of neovascularization within carotid plaques, and the presence of neovascularization may correlate with plaque morphology.

Effects of macrophage migration inhibitory factor on cardiac reperfusion injury in mice with depression induced by constant-darkness.

RATIONALE: Depression is associated with coronary artery disease and increases adverse outcomes and mortality in patients with acute myocardial infarction, but the underlying pathophysiological mechanisms remain unclear. OBJECTIVE: To evaluate the effect of macrophage migration inhibitory factor (MIF) on cardiac ischemia-reperfusion (I/R) injury in mice with constant darkness-induced depression. METHODS AND RESULTS: Twenty C57BL/6 mice (8 weeks old, male) were randomly divided into 2 groups: one group was housed in a 12h light/dark cycle environment (LD) and the other in a constant darkness environment (DD). After 3 weeks, constant darkness-exposed (DD) mice displayed depression-like behavior as indicated by increased immobility in the forced swim test (FST) and lower sucrose preference rate. Western blotting revealed cardiac MIF expression was significantly lower in the DD mice than that in the LD mice. Next, 84 mice were randomly divided into 4 groups: LD sham group, LD I/R group, DD sham group, and DD I/R group. Following ischemia and reperfusion, mice in the DD I/R group had a larger infarct area and lower heart function index than mice in the LD I/R group (P < 0.05 for both). The cardiac pAMPK and pACC expression levels of the DD I/R group were also lower in the DD I/R group (P < 0.05). CONCLUSION: DD-induced depression might cause decreased expression of MIF in the heart, resulting in downregulation of MIF-AMPK signaling and a subsequent adverse outcome after a cardiac I/R injury.

[Effects of Danshen on number and activity of endothelial progenitor cells of patients with hypercholesterolemia].

OBJECTIVE: To investigate the effects of Danshen on number and activity of endothelial progenitor cells (EPCs) of patients with Hypercholesterolemia. METHOD: 24 patients with Hypercholesterolemia were randomLy divided into 2 groups: control group (n = 12), and treatment group (n = 12, receiving Composite Denshen Pilulae, 10# tid for 2 weeks). after 2 weeks, 20 mL peripheral blood was obtained from each patient, Mononuclear fraction of human peripheral blood was obtained by density gradient centrifugation, plated on fibronectin coated culture dishes. The cells were identified by immunohistochemistry and flow cytometry and tested the ability to intake ac-LDL. Cell clusters were viewed with an inverted microscope, fluorescence-activated cell sorting (FACS) analysis of PE-CD34 and FITC-AC133 was performed to detect number of EPCs, EPC proliferation and migration were assayed with MTT assay, modified Boyden chamber assay. EPCs adhesion ability assay was performed by replating cells on fibronectin-coated dishes, and then counting adherent cells. RESULT: Numbers of EPCs (10(3) cells per 1 mL peripheral blood) of treatment group was higher than control group (7.20 +/- 1.29 vs 6.88 +/- 1.00). Compared with group control, numbers of clusters (per 40 power microscopic field), adhesive EPCs (per 400 power microscopic field) and migratory EPCs (per 200 power microscopic field) of treatment group were significantly increased (4.47 +/- 0.94 vs 3.38 +/- 0.57, P <0.01, 11.81 +/- 2.29 vs 10.03 +/- 1.32, P <0.05 and 15.75 +/- 2.27 vs 11.95 +/- 1.28, P <0.01, respectively), while OD vallue of treatment group were significantly increased too (0.27 +/- 0.04 vs 0. 20 +/- 0.03, P < 0.01). CONCLUSION: Danshen can significantly enhance EPCs functional activity of patients with Hypercholesterolemia.

Ox-LDL induces dysfunction of endothelial progenitor cells via activation of NF-κB.

Dyslipidemia increases the risks for atherosclerosis in part by impairing endothelial integrity. Endothelial progenitor cells (EPCs) are thought to contribute to endothelial recovery after arterial injury. Oxidized low-density lipoprotein (ox-LDL) can induce EPC dysfunction, but the underlying mechanism is not well understood. Human EPCs were cultured in endothelial growth medium supplemented with VEGF (10 ng/mL) and bFGF (10 ng/mL). The cells were treated with ox-LDL (50 µg/mL). EPC proliferation was assayed by using CCK8 kits. Expression and translocation of nuclear factor-kabba B (NF-κB) were evaluated. The level of reactive oxygen species (ROS) in cells was measured using H2DCF-DA as a fluorescence probe. The activity of NADPH oxidase activity was determined by colorimetric assay. Ox-LDL significantly decreased the proliferation, migration, and adhesion capacity of EPCs, while significantly increased ROS production and NADPH oxidase expression. Ox-LDL induced NF-κB P65 mRNA expression and translocation in EPCs. Thus ox-LDL can induce EPC dysfunction at least by increasing expression and translocation of NF-κB P65 and NADPH oxidase activity, which represents a new mechanism of lipidemia-induced vascular injury.

Shengmai injection, a traditional chinese patent medicine, for intradialytic hypotension: a systematic review and meta-analysis.

Intradialytic hypotension (IDH) is a global public health problem. A rising number of IDH sufferers resort to Chinese patent medicine, Shengmai Injection (SMI) in China. The objectives of present study are to assess the effectiveness and safety of SMI as an adjunct therapy for IDH. A systematic search of 6 medical databases was performed up to December 2011. Randomized trials involving SMI adjuvant therapy versus conventional therapy were identified. RevMan 5.0 was used for data analysis. Ten randomized clinical trials with 437 participants were identified. Methodological quality was considered inadequate in all trials. Compared with conventional therapy, SMI adjunct therapy showed significant effects in improving the clinic effective rate (P < 0.01), decreasing the incidence of IDH episode (P < 0.01), decreasing the frequency of nursing interventions (P < 0.01), and increasing diastolic blood pressure (P < 0.01). There was no statistical significance in the improvement of mean arterial pressure (P = 0.22) and systolic blood pressure (P = 0.08) between two groups. Four studies had mentioned adverse events, but no serious adverse effects were reported in any of the included trials. In conclusion, SMI adjunct therapy appears to be potentially effective in treatment of IDH and is generally safe. However, further rigorous designed trials are needed.

Factors associated with decision time for patients with ST-segment elevation acute myocardial infarction.

Increased delay in visiting a hospital for patients with ST-segment elevation myocardial infarction (STEMI) is often associated with poor outcomes. The factors associated with the decision time were analyzed by comparing the characteristics of patients with delays longer or shorter than the median of 60 min. Pre-hospital delay tended to be longer for patients living in suburban areas compared to those in urban areas (P=0.015). Shorter decision time was more likely among older patients. Being married, medical insurance coverage, and the level of educational qualification did not affect decision time. More efforts should be paid to educate the patients with high risk in suburban areas in order to effectively reduce pre-hospital delays.

Danshen protects endothelial progenitor cells from oxidized low-density lipoprotein induced impairment.

In this study, we examined the protective effects of Danshen both on endothelial progenitor cells (EPCs) in patients with hypercholesterolemia and on in-vitro EPCs of healthy volunteers. In the clinical study, we randomly divided 24 subjects with hypercholesterolemia into two groups (the control group and the Danshen-treated group). At the end of two weeks of treatment, the EPC cellular functions of both groups were tested. The results indicated that, compared to the control group, EPCs in the Danshen-treated group showed significantly better cellular functions, which was manifested in the cloning number, the proliferation capacity, the number of EPC adhesions, and cell migration. In the subsequent in-vitro experiments, EPCs were treated with vehicle, oxidized low-density lipoprotein (Ox-LDL, 100 microg/ml), or Ox-LDL (100 microg/ml) plus different concentrations of Danshen (Danshensu 2, 10, or 50 microg/ml, respectively) for 24 h. The results showed that Danshen treatments can prevent the detrimental effects of Ox-LDL on EPC cellular functions measured by proliferation capacity (0.24+/-0.08, 0.37+/-0.11, 0.30+/-0.04 vs. 0.13+/-0.02, P<0.05, P<0.01, and P<0.01, respectively), and adhesion ability (63.00+/-11.60, 70.00+/-10.80, 85.50+/-11.41 vs. 40.50+/-6.85, all P<0.01). Compared to the group treated with Ox-LDL alone, Danshen treatment significantly decreased the lipid peroxidation end product malondialdehyde (MDA) [(4.34+/-0.54), (3.98+/-0.47), (3.46+/-0.31) vs. (5.57+/-0.64) nmol/ml, all P<0.01], increased the production of superoxide dismutase (SOD) [(29.74+/-0.71), (31.09+/-0.83), (30.41+/-0.65) vs. (14.76+/-3.99) U/ml, all P<0.01], and lowered the expression of interleukin-6 (IL-6) [(24.62+/-7.69), (27.04+/-3.14), (33.38+/-18.86) vs. (230.67+/-33.53) pg/ml, all P<0.01] and tumor necrosis factor-alpha (TNF-alpha) [(41.72+/-6.10), (17.02+/-6.82), (3.73+/-2.26) vs. (228.71+/-41.53) pg/ml, all P<0.01] in Ox-LDL treated EPCs. These results suggest that Danshen may exert a protective effect through its antioxidant and anti-inflammatory features.

Carvedilol treatment ameliorates acute coxsackievirus B3-induced myocarditis associated with oxidative stress reduction.

Oxidative stress has been implicated in the pathogenesis of acute myocarditis. The imbalance between the occurrence of reactive oxygen species and the cellular antioxidant defense mechanism plays a key role in myocardial injury of viral myocarditis. Carvedilol, a nonselective beta-adrenoceptor antagonist with additional alpha1-adrenergic blocking and antioxidant properties, has been shown to be cardioprotective in experimental myocarditis. However, the expression of 4-hydroxy-2-nonenal (4-HNE), the most reliable marker of lipid peroxidation, has not been studied, and the antioxidative effects of carvedilol have not been investigated in the setting of acute viral myocarditis. This study was therefore designed to determine whether levels of lipid peroxides are elevated in the myocardium and whether carvedilol reduces the lipid peroxidation level and increases antioxidant enzyme activities. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of carvedilol and metoprolol on 14-day survival rate, myocardial histopathological changes, cardiac function, the expression of 4-HNE, virus titers, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidases (GSH-Px) activities were studied. Lipid peroxidations including 4-HNE and MDA, were elevated in murine coxsackievirus-induced acute viral myocarditis. Carvedilol, but not metoprolol, improved survival, reduced lipid peroxidations including 4-HNE and MDA, and increased antioxidant enzyme activities including SOD and GSH-Px with amelioration of acute viral myocarditis. These results show that carvedilol but not metoprolol exerts some of its beneficial effects by inhibiting peroxidants.