Microparticles from Patients with the Acute Coronary Syndrome Impair Vasodilatation by Inhibiting the Akt/eNOS-Hsp90 Signaling Pathway.

OBJECTIVES: Endothelial dysfunction is involved in the development of the acute coronary syndrome (ACS). Plasma microparticles(MPs) from other diseases have been demonstrated to initiate coagulation and endothelial dysfunction.However, whether MPs from ACS patients impair vasodilatation and endothelial function remains unclear. METHODS: Patients(n = 62) with ACS and healthy controls (n = 30) were recruited for MP isolation. Rat thoracic aortas were incubated with MPs from ACS patients or healthy controls to determine the effects of MPs on endothelial-dependent vasodilatation,the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS), the interaction of eNOS with heat shock protein 90 (Hsp90), and nitric oxide (NO) and superoxide anion(O 2 ­ ) production. The origin of MPs was assessed by flow cytometry. RESULTS: MP concentrations were increased in patients with ACS compared with healthy controls. They were positively correlated with the degree of coronary artery stenosis. MPs from ACS patients impair endothelial-dependent vasodilatation, decrease both Akt and eNOS phosphorylation,decrease the interaction between eNOS and Hsp90,and decrease NO production but increase O 2 ­ generation in rat thoracic aortas. Endothelial-derived MPs and platelet-derived MPs made up nearly 75% of MPs. CONCLUSIONS: Our data indicate that MPs from ACS patients negatively affect endothelial-dependent vasodilatation via Akt/eNOS-Hsp90 pathways.

Micelle-embedded coating with ebselen for nitric oxide generation.

Nitric oxide generation is considered to be a key factor to mimic endothelial function in terms of anti-coagulation and anti-hyperplasia. Herein, ebselen which could play the similar role as glutathion peroxidase-like was loaded into micelles and was further assembled into a layer-by-layer coating. The ability of nitric oxide generation and corresponding biological effect were investigated. Endothelial-mimetic surface has now attracted huge attention in blood-contacting materials, due to its inherent ability of secreting nitric oxide. Among those categories, nitric oxide generation surface is considered to be safe and tunable in the modification of vascular biomedical devices. How to adsorb or immobilize glutathion peroxidase-like catalyst and maintain sustained/safe nitric oxide generation is full of interest. This study aimed at developing a functional coating constructed via layer-by-layer assembly to introduce the catalyst into the coating by pre-loading ebselen in micelles. We firstly introduced phenylboronic acid moiety into the micelle molecule backbone and grafted catechol moiety to chitosan backbone. Then, chitosan, micelles (containing ebselen) and heparin were adopted as polyelectrolytes and then alternatively assembled onto the substrate via layer-by-layer protocol. The catechol was conjugated to the amine groups of chitosan by Schiff base reaction to synthesize chitosan-catechol. The hydrophobic cholesterol was conjugated to the one end of the hydrophilic hyaluronic acid, and the hydroxymethylphenylboronic acid was conjugated to the other end via the esterification of carboxyl (-COOH) and hydroxyl (-OH). The modified hyaluronic acid could spontaneously form micelles in aqueous solution. Ebselen was the loaded into the as-prepared micelles. Chitosan-catechol, heparin, and micelles were alternatively assembled onto the substrate layer by layer to form a micelle-embedded coating. The micelle-embedded coating with ebselen was successfully obtained and the nitric oxide generation ability was in a safe level which was close to healthy endothelial cells. The coating could effectively inhibit platelet adhesion and smooth muscle cell proliferation. The use of ebselen preloaded into micelles could provide a sustained release of catalyst for in situ nitric oxide generation. Besides, this method could also be used to load diverse drugs and regulate desired properties. The study was approved by the Institutional Review Board of the West China Hospital in Sichuan University on March 3, 2018, with approval No. K2018044.

[Association of the beta2-adrenergic receptor gene C659G polymorphism and essential hypertension in Xinjiang Kazakans.].

OBJECTIVE: To investigate the relationship between human beta2-Adrenergic Receptor (ADRB2) gene C659G polymorphism and essential hypertension in Xinjiang Kazakans. METHODS: Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) methods were used to detect the C659G polymorphism of ADRB2 gene in 435 Kazakans including 273 hypertensives (EH) and 162 normotensives (NT) and genotype frequencies between EH and NT were analyzed. RESULTS: The genotype frequencies (CC, CG, GG) of the C659G allele were 85.75%, 13.79%, 0.64% respectively and the C659 and G659 allele frequencies were 7.36%, 92.64% in this cohort. The ADRB2 genotype distribution and the allele frequencies of C659 and G659 were significantly higher in EH than those in NT (all P < 0.05). The G allele is a risk factor contributed to hypertension (OR 12.37). After adjustment for age and BMI, the systolic and diastolic blood pressure levels were significant higher in CG + GG genotype group compared with CC genotype group (P < 0.05). CONCLUSION: There was significant association between the C659G polymorphism of ADRB2 gene and essential hypertension in Xinjiang Kazakans suggesting a role of ADRB2 gene C659G polymorphism in the development of hypertension in Xinjiang Kazakans.