Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Sep 2015
Protein Kinase C Isoforms Distinctly Regulate Propofol-induced Endothelium-dependent and Endothelium-independent Vasodilation.
Protein kinase C (PKC) isoforms improve endothelial nitric oxide synthase activity and contractile Ca sensitivity in blood vessels. These actions may have opposite effects on propofol-induced vasodilation. This study examines the hypothesis that propofol induces relaxation by enhancing the PKC-mediated nitric oxide synthesis in endothelium and/or inhibiting the PKC-regulated Ca sensitivity in vascular smooth muscle (VSM). ⋯ Downregulation of novel isoforms not only reduced the norepinephrine-elicited contraction but also decreased the magnitude of propofol-induced relaxation. In vascular smooth muscle cells, propofol prevented norepinephrine-elicited phosphorylation of myosin light chain. Propofol can increase the PKC-mediated availability of nitric oxide but inhibit the novel PKC-regulated Ca-sensitization, which provides a novel explanation for the mechanism of propofol-induced vasodilation.
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J. Cardiovasc. Pharmacol. · Sep 2015
Review Meta AnalysisNeutrophil Gelatinase-associated Lipocalin in the Prediction of Contrast-induced Nephropathy: A Systemic Review and Meta-analysis.
The aim of this study was to investigate the predictive value of neutrophil gelatinase-associated lipocalin (NGAL) in the early diagnosis of contrast-induced nephropathy (CIN). ⋯ Plasma/serum and urinary NGAL levels seem to be useful biomarkers in the early prediction of CIN. Moreover, urinary NGAL levels perform better than plasma/serum NGAL.
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J. Cardiovasc. Pharmacol. · Jul 2015
MicroRNA-204 Targets Runx2 to Attenuate BMP-2-induced Osteoblast Differentiation of Human Aortic Valve Interstitial Cells.
Osteoblast differentiation of valve interstitial cells (VICs) is a key step in valve calcification, but the molecular mechanisms involved are not fully understood. In this study, we aimed to investigate whether microRNA (miR)-204-regulated VICs differentiation through modulation of runt-related transcription factor 2 (Runx2), a key transcription factor for osteogenesis. Our data demonstrated that miR-204 was markedly downregulated in both human calcified aortic valves and bone morphogenetic protein (BMP)-2-stimulated aortic VICs. ⋯ Luciferase reporter assays validated Runx2 as the direct target of miR-204. Furthermore, increased alkaline phosphatase activity and osteocalcin expression after miR-204 inhibition were abolished by small interfering RNA-mediated silencing of Runx2. Overall, these data suggested miR-204 as a possible molecular switch inhibiting osteoblastic transdifferentiation of human aortic VICs and targeting miR-204 may have therapeutic potential for human aortic valve calcification.
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J. Cardiovasc. Pharmacol. · Jun 2015
Randomized Controlled Trial Comparative StudyEffect of Ivabradine on Heart Rate and Duration of Exercise in Patients With Mild-to-Moderate Mitral Stenosis: A Randomized Comparison With Metoprolol.
Symptoms in mitral stenosis (MS) are heart rate (HR) dependent. Increase in HR reduces diastolic filling period with rise in transmitral gradient. By reducing HR, beta-blockers improve hemodynamics and relieve symptoms, but the use may be limited by side effects. The present randomized crossover study looked at comparative efficacy of ivabradine and metoprolol on symptoms, hemodynamics, and exercise parameters in patients with mild-to-moderate MS (mitral valve area, 1-2 cm) in normal sinus rhythm. ⋯ Both metoprolol and ivabradine reduced symptoms and improved hemodynamics significantly from baseline to a similar extent. Ivabradine thus can be used effectively and safely in patients with MS in normal sinus rhythm who are intolerant or contraindicated for beta-blocker therapy.
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J. Cardiovasc. Pharmacol. · Mar 2015
Oral L-carnitine supplementation increases trimethylamine-N-oxide but reduces markers of vascular injury in hemodialysis patients.
Food or supplement-derived L-carnitine is changed to trimethylamine (TMA) by interstinal microbiota, which is further metabolized to trimethylamine-N-oxide (TMAO), being involved in the promotion of atherosclerosis in animal models. Meanwhile, carnitine deficiency has played a role in accelerated atherosclerosis in hemodialysis (HD) patients. However, effects of oral L-carnitine supplementation on circulating levels of TMAO and markers of vascular injury and oxidative stress in patients on HD remain unclear. In this study, we addressed the issue. ⋯ This study demonstrated that although oral L-carnitine supplementation was associated with increased TMAO levels, it might be beneficial on vascular injury in patients on HD. Vasculoprotective properties of L-carnitine supplementation in HD patients might be ascribed partly to its inhibitory actions on AGE.