International heart journal
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The present meta-analysis aimed to evaluate effects of tolvaptan on fluid retention in patients with heart failure who were non-responsive to conventional treatment and to assess differences between effects of low (≤ 15 mg/day) and high (> 15 mg/day) tolvaptan doses. Randomized controlled trials comparing add-on tolvaptan therapy and placebo or therapy with other diuretics in patients with heart failure were identified through a database search. The primary outcomes were changes in body weight and urine volume, and the secondary outcomes were changes in serum sodium and creatinine levels. ⋯ Serum creatinine levels slightly increased in the high-dose group (MD, 0.06; 95% CI, 0.04 to 0.08) and slightly decreased in the low-dose group (MD, -0.10; 95% CI, -0.19 to -0.01). Our findings suggest that add-on tolvaptan therapy for heart failure improves fluid retention in the early therapy phase. However, this drug should be properly used to avoid the worsening of renal function, which may occur at high doses.
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The phenotype shifting of vascular smooth muscle cells (VSMCs) was indicated to play a role during the initial stage of atherosclerotic plaque formation by facilitating extracellular matrix deposition. This study was aimed at investigating the involvement of the apoptosis signal-regulating kinase 1 (ASK1) /mitogen-activated protein kinase (MAPK) kinases (MKKs) /p38 MAPK pathway in the advanced glycation end product (AGE) -induced fibrotic response of VSMCs. The effect of the novel ASK1 inhibitor AGI-1067 was also studied. ⋯ AGI-1067 administration not only dramatically inhibited the activation of ASK1/MKKs/p38 MAPK but also suppressed the expression of the downstream proteins, including transforming growth factor-β1, connective tissue growth factor, collagen I, and collagen VIII in HCSMCs exposed to AGEs. The ASK1/MKKs/p38 MAPK pathway was activated by AGEs, leading to the fibrotic response in VSMCs. AGI-1067 reversed this process by maintaining the inactive state of ASK1.