Combined glycoprotein IIb/IIIa inhibitor therapy with ticagrelor for patients with acute coronary syndrome.

This study was to compare the efficacy and safety of combined glycoprotein IIb/IIIa inhibitor (GPI) and ticagrelor versus ticagrelor in patients with acute coronary syndrome (ACS). An observational study was conducted using the Improving Care for Cardiovascular Disease in China-ACS project. Totally, 13,264 patients with ACS and received combination therapy or ticagrelor therapy were analyzed. The primary outcome was the composite of major cardiovascular events (MACE: all-cause mortality, myocardial infarction [MI], stent thrombosis, cardiogenic shock, and ischemic stroke), and secondary outcomes included all-cause mortality, MI, stent thrombosis, cardiogenic shock, and ischemic stroke. The multivariable adjusted analysis indicated that combination therapy was associated with an increased risk of major cardiovascular events (MACE) (P = 0.001), any bleeding (P<0.001), and major bleeding (P = 0.005). Moreover, the multivariable adjusted for propensity score-matched (PSM) analysis suggested that combination therapy produced additional risk of MACE (P = 0.014), any bleeding (P<0.001), and major bleeding (P = 0.005). Moreover, PSM analysis suggested that combination therapy was associated with greater risk of stent thrombosis (P = 0.012) and intracranial bleeding (P = 0.020). Combined GPI and ticagrelor therapies did not have any beneficial effects on MACE, stent thrombosis, intracranial bleeding, any bleeding, or major bleeding.

The Inhibition of Oxidised Low-Density Lipoprotein-Induced Apoptosis of Macrophages by Recombinant Human Brain Natriuretic Peptide and the Underlying Mechanism.

OBJECTIVE: Macrophage apoptosis plays a key role in atherosclerotic plaque rupture. This study investigated the effects of recombinant human brain natriuretic peptide (BNP) on oxidised low-density lipoprotein (ox-LDL)-induced macrophage apoptosis and explored the underlying mechanism. METHODS: A model of ox-LDL-induced macrophage injury was established to evaluate the role of BNP. Flow cytometry was employed to detect apoptosis and changes in mitochondrial membrane potential (x0394;x03A8;m), and confocal microscopy was used to determine cellular reactive oxygen species (ROS) levels. Additionally, reverse transcription-polymerase chain reaction and colourimetry were used to detect the mRNA expression and activity, respectively, of superoxide dismutase (SOD) and malondialdehyde (MDA). RESULTS: Ox-LDL induced macrophage apoptosis in a concentration-dependent manner, and maximum apoptosis occurred at 100 µg/ml ox-LDL (45.62 ± 2.76 vs. 6.84 ± 1.94%; p < 0.05). Conversely, BNP suppressed macrophage apoptosis, with a maximal effect at 10-9 mol/l (18.56 ± 1.79%; p < 0.05). Compared with the control group, intracellular ROS levels increased, x0394;x03A8;m decreased, SOD mRNA expression and activity decreased and MDA mRNA expression and content increased in the 100-µg/ml ox-LDL group (527.30 ± 36.20 vs. 100.00 ± 0.00%, 3.01 ± 0.52 vs. 9.67 ± 0.51%, 0.53 ± 0.18 vs. 1.00 ± 0.00, 256.6 ± 8.20 vs. 355.8 ± 9.58 U/ml, 1.59 ± 0.23 vs. 1.00 ± 0.00 and 29.4 ± 1.68 vs. 5.94 ± 0.51 nmol/ml; p < 0.05); these effects were significantly counteracted by 10-9 mol/l BNP (237.30 ± 30.62%, 6.55 ± 1.57%, 0.90 ± 0.07, 310.4 ± 2.97 U/ml, 1.14 ± 0.10, 20.54 ± 1.55 nmol/ml; p < 0.05). CONCLUSION: BNP attenuates ox-LDL-induced macrophage apoptosis by suppressing oxidative stress and preventing x0394;x03A8;m loss.

Construction of a recombinant adenovirus carrying endothelial nitric oxide synthase gene and its expression and control in esophageal smooth muscle cells.

OBJECTIVE: Nitric oxide (NO) is a major inhibitory neurotransmitter, and its deficiency plays an important role in the pathogenesis of motility disorders of the gastrointestinal tract. The present study was designed to generate a recombinant adenovirus containing the tetracycline (Tet)-regulated endothelial nitric oxide synthase (eNOS) gene and to detect the controllable expression of the gene in esophageal smooth muscle cells (ESMC). METHODS: The construction of the recombinant adenovirus was completed in three steps: (1) a Tet-responsible expression cassette was made by cloning the full-length cDNA encoding eNOS into a pTRE-Shuttle Vector, which can be regulated by tetracycline or its analogs, such as doxycycline (Dox); (2) the expression cassette was transferred to Adeno-X viral DNA to form a recombinant adenoviral plasmid (pAd-eNOS) by means of an in vitro ligation reaction; and (3) the Ad-eNOS was packaged into infectious adenoviral particles (Adeno-X-TRE-eNOS) by transfecting human embryonic kidney (HEK) 293 cells. Cultured ESMC were coinfected by Adeno-X-TRE-eNOS and regulation virus (Adeno-X Tet-off virus), and the Dox-regulated eNOS expression was detected by RT-PCR and western blot. RESULTS: The recombinant adenovirus (Adeno-X-TRE-eNOS) was generated successfully by an in vitro ligation reaction. The expression of the eNOS gene in the coinfected ESMC was confirmed by RT-PCR and western blot. Furthermore, the transcription could be precisely regulated in a dose-dependent manner in a series of concentrations of Dox, and it was completely turned off when the concentration reached 0.01 microg/mL. CONCLUSIONS: A Tet- (or Dox-) regulated recombinant adenovirus carrying eNOS was successfully generated and controllable expression of eNOS in ESMC was achieved, which provides some material for conducting further gene therapy studies with eNOS.