Endothelial nitric oxide synthase enhancer AVE3085 reverses endothelial dysfunction induced by homocysteine in human internal mammary arteries

Publication date: Available online 6 October 2018Source: Nitric OxideAuthor(s): Hai-Tao Hou, Jun Wang, Xi Zhang, Zheng-Qing Wang, Tie-Nan Chen, Jian-Liang Zhang, Qin Yang, Guo-Wei HeAbstractHomocysteine (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 vessel...
Source: Nitric Oxide - Category: Chemistry Source Type: research