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Ha, C.H.,Kim, S.,Chung, J.,An, S.H.,Kwon, K. Elsevier/North-Holland Biomedical Press 2013 INTERNATIONAL JOURNAL OF CARDIOLOGY Vol.168 No.4
Background: Extracorporeal shock wave has been used in the noninvasive treatment of various diseases including musculoskeletal disorders. In particular, shock wave with low energy level showed anti-inflammatory effect and increased angiogenesis in ischemic tissues. However, the detailed cellular pathway in endothelial signaling is not fully understood. We investigate the role of shock wave with low energy level in angiogenic gene expression and underlying molecular mechanism by comparing the laminar and oscillatory fluid shear stresses in endothelial cells. Methods and results: We show that shock wave with low energy level (0.012-0.045mJ/mm<SUP>2</SUP>) stimulated phosphorylation of Akt, eNOS and Erk ½ in a time-dependent manner which is similar to the effect of laminar fluid shear stress. The transfection of endothelial cells with siRNA encoding VEGFR2, VE-cadherin and PECAM-1 inhibited shock wave-induced phosphorylation of Akt, eNOS and Erk ½ and angiogenic gene expressions, including Akt, eNOS, KLF2/4, and Nur77. Moreover, mechanical stimulation through extracorporeal shock wave induced endothelial cell migration and tube formation. Conclusions: Our results demonstrate that shock wave-induced Akt/eNOS phosphorylation and angiogenic gene expression were mediated through the mechanosensory complex formation involving VEGFR-2, VE-cadherin and PECAM-1 which was similar to the effect of laminar shear stress.
Yoon, Kun‐,Ho,Nishimura, Rimei,Lee, Jisoo,Crowe, Susanne,Salsali, Afshin,Hach, Thomas,Woerle, Hans J. Blackwell Publishing Ltd 2016 DIABETES OBESITY AND METABOLISM Vol.18 No.10
<P>We investigated the efficacy and safety of empagliflozin over 24 weeks in Asian patients with type 2 diabetes (T2DM) using pooled data from four phase III trials. In these trials, patients were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg or placebo as monotherapy or add‐on to metformin, metformin plus sulphonylurea or pioglitazone ± metformin. In total, 1326 patients from Asia received ≥1 dose of study drug. At week 24, adjusted mean differences versus placebo in change from baseline in glycated haemoglobin (HbA1c) were −0.66% [95% confidence interval (CI) −0.76, −0.56] and −0.73% (95% CI −0.83, −0.64) and in weight were −1.6 kg (95% CI −1.9, −1.3) and −1.8 kg (95% CI −2.1, −1.5) with empagliflozin 10 and 25 mg, respectively (all p < 0.001). Empagliflozin significantly reduced systolic and diastolic blood pressure. The proportion of patients reporting ≥1 adverse event was similar across treatment groups, but events consistent with genital infection were more common in patients treated with empagliflozin 10 mg (3.4%) or 25 mg (2.3%) than placebo (0.9%). Thus in Asian patients with T2DM, empagliflozin reduced HbA1c, weight and blood pressure, and was well tolerated.</P>