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2.
Atherosclerosis ; 229(2): 287-94, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23880178

ABSTRACT

OBJECTIVE: The aim of present study was to test the hypothesis that activation of receptor for advanced glycation end products (RAGE) pathway contributes to aortic remodeling and endothelial dysfunction in sinoaortic denervated (SAD) rats. METHODS AND RESULTS: Experiment 1: 8 weeks after sinoaortic denervation, aortas were removed for measurement of AGE/RAGE pathway. Sinoaortic denervation in rats resulted in enhanced activity of aldose reductase, reduced activity of glyoxalase 1, accumulation of methylglyoxal and AGE, and upregulated expression of RAGE in aortas. Experiment 2: 5 weeks after sinoaortic denervation, the rats received intraperitoneal injections of 500 µg soluble RAGE (sRAGE) daily for 3 weeks. Treatment of SAD rats with sRAGE attenuated aortic remodeling, marked by reduction in AW/length, wall thickness, proliferation of SMC, and collagen deposition, and improvement of endothelial function. Treatment of SAD rats with sRAGE abated aortic oxidative stress, marked by reduction in formation of malondialdehyde, reactive oxygen species, superoxide, peroxynitrite and 3-nitrotyrosine, and enhancement of ratio of GSH/GSSG. Treatment of SAD rats with sRAGE attenuated aortic mitochondrial dysfunction. Treatment of SAD rats with sRAGE suppressed aortic NFκB nuclear translocation and inflammation. Treatment of SAD rats with sRAGE restored aortic NO formation through upregulating eNOS and dimethylarginine dimethylaminohydrolase-2 and downregulating protein arginine methyltransferase-1. CONCLUSION: Activated RAGE contributed to aortic remodeling and endothelial dysfunction in SAD rats, possibly via induction of oxidative stress and inflammation, impairment of mitochondrial function, and reduction in NO bioavailability.


Subject(s)
Aorta/metabolism , Autonomic Denervation , Cardiovascular Diseases/metabolism , Endothelium, Vascular/metabolism , Receptors, Immunologic/metabolism , Vasculitis/metabolism , Aldehyde Reductase/metabolism , Animals , Aorta/innervation , Aorta/physiopathology , Baroreflex/physiology , Cardiovascular Diseases/physiopathology , Disease Models, Animal , Endothelium, Vascular/innervation , Endothelium, Vascular/physiopathology , Lactoylglutathione Lyase/metabolism , Male , Mitochondria/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type III/metabolism , Oxidative Stress/physiology , Rats , Rats, Sprague-Dawley , Receptor for Advanced Glycation End Products , Vasculitis/physiopathology
3.
Acta Cardiol ; 68(6): 621-6, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24579441

ABSTRACT

OBJECTIVE: The object of this study was to investigate the possible role of local voltage potentials (LVPs) in mapping the ventricular arrhythmias originating from right ventricular outflow (RVOT). METHODS: Forty-seven patients with RVOT VAs (ventricular arrhythmias), referred for radiofrequency catheter ablation to our hospital, were analysed retrospectively for the prevalence, characteristics and electrophysiological evaluation of the LVPs recorded in successful and unsuccessful ablation sites. RESULTS: Radiofrequency ablation was successful immediately in all the 47 cases. Catheter ablation was performed at a mean of 8 +/- 6 sites per patient. There were 58 effective ablation sites, 5 cases with changing morphology of ventricular arrhythmias (VAs), and 318 invalid ablation sites. Activation times at effective ablation sites were slightly earlierthan those at invalid ablation sites (-28 +/- 8 ms vs-24 +/- 7 ms, P < 0.05). The LVPs appeared during VAs in 47 sites of the 58 effective ablation sites (81.0%), far more than the 22 sites of the 318 invalid ablation sites (6.9%) (P < 0.01). In two cases VAs recurred during follow-up. They received a second catheter ablation. CONCLUSIONS: Local ventricular potentials can be recorded in most patients with idiopathic VAs originating from the right outflow tract.The local potentials may facilitate successful radiofrequency ablation.


Subject(s)
Action Potentials/physiology , Electrocardiography , Heart Conduction System/physiopathology , Tachycardia, Supraventricular/physiopathology , Adult , Catheter Ablation , Female , Follow-Up Studies , Humans , Male , Retrospective Studies , Tachycardia, Supraventricular/surgery
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