کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
11263191 1746590 2018 32 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Endothelial nitric oxide synthase enhancer AVE3085 reverses endothelial dysfunction induced by homocysteine in human internal mammary arteries
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Endothelial nitric oxide synthase enhancer AVE3085 reverses endothelial dysfunction induced by homocysteine in human internal mammary arteries
چکیده انگلیسی
Homocysteine (Hcy) is an independent risk factor for endothelial dysfunction in cardiovascular diseases. We hypothesized that the eNOS transcription enhancer AVE3085 may protect the endothelial function damaged by Hcy in the human internal mammary artery (IMA). Cumulative concentration-relaxation curves to acetylcholine (−10 to −4.5 log mol/L) or sodium nitroprusside were established in IMA from patients undergoing coronary artery surgery precontracted by U46619 (−8 log mol/L) in the absence/presence of Hcy (100 μmol/L) with/without AVE3085 (30 μmol/L) in vitro in a myograph. RT-qPCR and ELISA were used to quantify the mRNA and protein levels of eNOS. Colorimetric assay method was used to detect the production of nitric oxide (NO). Maximal relaxation was significantly attenuated by Hcy in human IMA. Co-incubation with AVE3085 protected endothelium from the impairment by Hcy and increased the production of NO. Exposure to Hcy for 24 h downregulated eNOS protein expression (P < 0.05) whereas it upregulated the expression of eNOS at mRNA levels (P < 0.05). The presence of AVE3085 in addition to Hcy significantly increased the eNOS protein (P < 0.05) and slightly decreased the mRNA level. The study for the first time revealed that in the human blood vessels (IMA) the clinically-relevant high concentration of Hcy directly causes endothelial dysfunction by downregulating eNOS protein that may be reversed by AVE3085. These findings not only provide new direction for protecting endothelium during coronary artery bypass grafting and improving long-term patency of the grafts, but also provide evidence to the use of eNOS enhancer in the patients with endothelial dysfunction in various pathological conditions.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Nitric Oxide - Volume 81, 1 December 2018, Pages 21-27
نویسندگان
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