Combination of exendin-4 and DPP-4 silencing promoted angiogenesis of human coronary artery endothelial cells via activation of PI3K/Akt pathway.

This study was aimed to explore the combined effects of Exendin-4 with dipeptidyl peptidase-IV (DPP-4) silencing on vascular endothelial growth factor (VEGF)-induced cell proliferation and angiogenesis in Human Coronary Artery Endothelial Cells (HCAECs), as well as the underlying molecular mechanisms which were involved in this process. HCAECs were treated by exendin-4, small interfering RNA (siRNA) targeting DPP-4 (DPP-4-siRNA) or exendin-4 plus DPP-4-siRNA, respectively. Cell migration, proliferation and angiogenesis in vitro were assessed by scratch-wound assay, MTT, tran swell assay, and matrigel tube formation, respectively. Cell apoptosis was investigated by TUNEL assay. Expression of apoptosis and PI3K/Akt related proteins were assessed by Western blotting. Incubation of HCAECs with exendin-4 and silencing of DPP-4 both caused an increase in cell proliferation, migration and tube formation, while a significant decrease in apoptosis (all p<0.05). Furthermore, the combination of the exendin-4 and silencing of DPP-4 had additional effects on HCAECs. Protein levels of p-Akt and p-PI3K were markedly increased by exendin-4 incubation, silencing of DPP-4 in HCAECs. These results suggest that combination of exendin-4 and silencing of DPP-4 had additional promoted effects on angiogenesis of HCAECs via activation of PI3K/Akt pathway. Our study indicated an alternative therapeutic strategy for atherosclerotic neovascularization.

In vitro, ex vivo and in vivo anti-hypertensive activity of Chrysophyllum cainito L. extract.

Chrysophyllum cainito L., a traditional herbal medicine, could have the potential for management of hypertension due to presence of polyphenolic compounds. The extracts and fractions of the pulp of plant were evaluated for in vitro (inhibition of angiotensin I converting enzyme/ACE assay), ex vivo (isolated aorta relaxation assay) and in vivo (salt induced hypertensive rat assay). The alcoholic and aqueous extract (ALE and AQE respectively) of fruit of plant C. cainito was having 14.8 and 9.2% yield respectively. The fractionation with ethyl alcohol (EAF) and butanol (BTF) yielded 2.52 & 2.17% respectively from ALE and 0.46 & 0.31% respectively from AQE with respect to fruit pulp dry weight. More phenolic content was found in ALE (3.75±0.15 mg gallic acid equivalent or GAE g(-1) of dry power of fruit pulp) compared to AQE and maximum in ethyl acetate fraction of ALE (ALE-EAF) (2.32±0.21 mg GAE g(-1) of dry power of fruit pulp) among all fractions. ACE inhibition activity was found to be maximum in ALE-EAF 62.5±7.34%. While ex vivo study using isolated tissue of aorta showed again showed maximum activity (62.82±6.19 and 46.47±8.32% relaxation with 50 µg mL(-1) and 10 µg mL(-1) GAE concentration respectively). ALE-EAF reduced the elevated arterial pressure of salt induced hypertensive rat significantly to the level of normotensive animal group. Results of ALE-EAF have shown its potential as a source for novel constituent for the treatment hypertension and should further be studied for isolation of specific constituent for more effectiveness.

Anxiety disorders are associated with increased plasma adrenomedullin level and left ventricular hypertrophy in patients with hypertension.

OBJECTIVE: To investigate the association between anxiety disorders and left ventricular hypertrophy in patients with essential hypertension. METHODS: Left ventricular structure and function were assessed with echocardiography in 56 patients with essential hypertension and anxiety disorder (study group) and in 56 patients with hypertension only (control group). Serum adrenomedullin levels were also measured in these patients. RESULTS: There was no statistically significant difference in the left ventricular ejection fraction between the study and the control group (54.21 ± 88.81% versus 56.01 ± 7.85%, p>0.05). The left ventricular mass index (LVMI) in study group was higher than in control group (137.05 ± 9.42 versus 123.57 ± 7.01 g/m(2), p=0.001). The plasma levels of adrenomedullin in study group was higher than in control group (25.97 ± 5.48 versus 18.32 ± 6.97 ng/L, p=0.001). Levels of plasma adrenomedullin were positively correlated with LVMI in the study (r=0.734, p<0.05) and control group (r=0.592, p<0.05). CONCLUSION: Anxiety disorders are associated with elevated plasma adrenomedullin levels and increased left ventricular hypertrophy in patients with essential hypertension. The clinical significance of these changes requires further investigation.

Atorvastatin improves endothelial progenitor cell function and reduces pulmonary hypertension in patients with chronic pulmonary heart disease.

OBJECTIVE: To explore the effects of atorvastatin on the migration and adhesion of endothelial progenitor cells (EPCs) and on pulmonary artery pressure (PAP) in patients with chronic pulmonary heart disease. METHODS: A total of 68 patients with chronic pulmonary heart disease were randomly assigned to either a control group (n=35) or a treatment group (n=33). In addition, 30 healthy volunteers (17 male, 13 female) were enrolled as healthy controls. Atorvastatin (20 mg per day) was administered to the treatment group. The migration and adhesion activities of EPCs in peripheral blood were assessed before and six months after the treatment. PAP was measured using echocardiography before and after the treatment. RESULTS: EPC number, migration ability and adhesion activity in the peripheral blood of patients in the control and treatment groups were lower than in patients in the healthy control group at baseline (all P<0.05). After six months of atorvastatin therapy, the number of EPCs in the treatment group was greater than in the control group (P<0.05). Migration and adhesion functions of EPCs in the treatment group were greater than in the control group (all P<0.05). The reduction in PAP in the treatment group was greater than in the untreated control group following six months of therapy (P<0.05). CONCLUSION: Atorvastatin therapy increased the migration and adhesion activities of EPCs in patients with chronic pulmonary heart disease. Atorvastatin treatment was also associated with a reduction in PAP in these patients.

Effects of xuezhikang on proliferation and adhesion capacity of cultured endothelial progenitor cells: An in vitro study.

BACKGROUND: Endothelial progenitor cells (EPCs) might be useful in the management of coronary artery disease (CAD). OBJECTIVE: The aim of this study was to investigate the effects of xuezhikang, an extract of Chinese red yeast rice, on the proliferation and adhesion capacity of EPCs from the peripheral blood of patients with stable CAD. METHODS: Mononuclear cells from 20 Chinese patients (14 men, 6 women; mean [SD] age, 64.5 [2.8] years [range, 60-69 years]) were isolated using densitygradient centrifugation. After 4 days in culture, the attached cells were treated with different concentrations of xuezhikang (50, 125, 250, and 500 ng/mL; 20 samples/group), atorvastatin (10 ng/mL; n = 20), or phosphate-buffered saline (control, n = 20) for 3 days. Cells that were positive for 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labeled acetylated low-density lipoprotein and lectin were defined as EPCs. They were counted by 2 independent investigators in ≥4 randomly selected highpower fields per well. EPCs were then treated and adherent cells were counted by the independent investigators who were blinded to study drug administration. RESULTS: The mean (SD) number of cultured EPCs in the xuezhikang 50-, 125-, 250-, and 500-ng/mL groups (205 [28], 244 [31], 283 [42], and 334 [43] cells, respectively; all, P < 0.001) was significantly increased in a dose-dependent manner compared with the control group (167 [36] cells). The adhesion capacity of the EPCs was significantly greater in the 4 xuezhikang groups (51 [9], 62 [10], 71 [11], and 83 [12] cells; all, P < 0.001) when compared with that of the control group (41 [7] cells). Both the number of EPCs (327 [49] cells) and the number of adhesive EPCs (84 [15] cells) in the atorvastatin group were also significantly increased compared with the control group (both, P < 0.001); however, these increases were not significantly different from those in the xuezhikang 500-ng/mL group. CONCLUSIONS: Xuezhikang was associated with significantly enhanced proliferation and adhesion capacity of EPCs derived from the peripheral blood of these patients with stable CAD. These effects were not significantly different between xuezhikang and atorvastatin.

Generalized anxiety disorder and the circadian rhythm of blood pressure in patients with hypertension.

Objective. To investigate the impact of generalized anxiety disorder (GAD) on the circadian rhythm of blood pressure in patients with hypertension. Methods. The 24-h ambulatory blood pressure was compared between patients with hypertension and GAD, and patients with hypertension only. Results. The mean day- and night-time systolic (SBP, 156.6±11.0 and 149.6±12.4 mmHg, respectively) blood pressure in patients with GAD was greater than in the no-GAD group (143.2±15.0 and 126.0±10.8 mmHg, respectively, P<0.01). The mean day- and night-time diastolic blood pressure (DBP, 101.5±10.1 and 96.9±17.6 mmHg, respectively) in the GAD group was also greater than in the no-GAD group (94.1±10.9 and 77.4±10.2 mmHg, respectively, P<0.01). SBP and DBP dipping was found in 87.5 and 80.1% of the hypertension only patients, as compared with 16.6 and 21.4% respectively, of the hypertension and GAD patients (P<0.01). Conclusions. The presence of GAD is associated with a higher level of blood pressure in hypertensive patients. GAD is also associated with a diminished circadian rhythm of blood pressure. The clinical significance of the reduced blood pressure dipping at night requires further investigation.

L-carnitine as an adjunct therapy to percutaneous coronary intervention for non-ST elevation myocardial infarction.

OBJECTIVES: To evaluate the effects of L: -carnitine as an adjunct therapy to percutanenous coronary intervention (PCI) for non-ST elevation acute coronary syndrome (NSTEMI). MATERIALS AND METHODS: Ninety-six consecutive patients with NSTEMI were randomized into treatment group (L: -carnitine 5 g IV bolus followed by 10 g/day IV infusion for 3 days), and control group. All patients also underwent PCI within 24 h from the onset of chest pain. The peak values of creatine kinase-MB and troponin-I before and after PCI were observed. RESULTS: In the treatment group, the peak values of creatine kinase-MB were significantly lower than the control group at 12 h and 24 h after PCI (P < 0.01). The peak values of troponin-I in the treatment group were also lower than the control group at 8 h after PCI (P < 0.01). Multivariate regression analysis showed that L: -carnitine therapy was an independent predictor for the reduction of creatine kinase-MB (r = 0.596, P < 0.001) or troponin-I (r = 0.633, P < 0.001). CONCLUSION: L: -carnitine adjunct therapy appears to be associated with a reduced level of cardiac markers in patients with NSTEMI. These results support a larger clinical trial to investigate the effect of L: -carnitine on cardiac events following PCI.

Transesophageal cardioversion of atrial flutter and atrial fibrillation using an electric balloon electrode system.

OBJECTIVE: To determine the feasibility and efficiency of terminating atrial flutter (AFL) and atrial fibrillation (AF) using synchronous low-energy shocks delivered through a novel transesophageal electric balloon electrode system. METHODS: By using a novel electric balloon electrode system, we attempted 91 transesophageal cardioversions in 52 patients, to treat 53 episodes of AFL and 38 episodes of AF. RESULTS: Of the 40 patients of AFL that failed to respond to drug therapy, 37 (92.5%) were successfully countershocked to sinus rhythm by transesophageal cardioversion, with a mean energy of (22.70 +/- 4.50) J (20 - 30 J). Of the 19 patients in AF, transesophageal cardioversion was successful in 16 (84.2%) cases, requiring a mean delivered energy of (17.38 +/- 8.58) J (3 - 30 J). There were no complications such as heart block or ventricular fibrillation, and no evidence of esophageal injury. CONCLUSIONS: Transesophageal cardioversion using an electric balloon electrode system is an effective and feasible method for the treatment of AFL and AF. It requires low energy and no anesthesia, leads to less trauma, and shows a high cardioversion success rate that may prove valuable in the management of tachyarrhythmias.