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Protection of Endothelial Function from Homocysteine‐induced Injury by Endothelial Nitric Oxide Synthase Enhancer in Human Internal Mammary Artery
Author(s) -
Hou HaiTao,
Yang Qin,
Wang Jun,
Wang ZhengQing,
Chen TieNan,
Liu ZhiGang,
Liu XiaoCheng,
He GuoWei
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1065.7
Subject(s) - enos , endothelial dysfunction , medicine , downregulation and upregulation , homocysteine , endocrinology , endothelium , nitric oxide , chemistry , nitric oxide synthase , biochemistry , gene
Objective Homocysteine (Hcy) is a sulfur‐containing amino acid formed during the metabolism of methionine. Hcy is an independent risk factor for endothelial dysfunction in cardiovascular diseases and atherosclerosis in the general population. We hypothesized that the eNOS transcription enhancer AVE3085 might improve the endothelial function altered by Hcy in the human internal mammary artery (IMA). Methods Cumulative concentration‐relaxation curves to acetylcholine (−10 to −4.5 log mol/L) were established in IMAs (n=28) from patients undergoing coronary artery bypass grafting in the precontraction induced by U46619 (−8 log mol/L) in the absence or presence of Hcy (100 μmol/L) with/without AVE3085 (30 μmol/L) in vitro in a myograph. Quantitative real‐time reverse transcription–polymerase chain reactions (RT‐qPCR) and enzyme‐linked immunosorbent assay (ELISA) were used to quantify the mRNA and protein levels of eNOS. Results Maximal relaxation induced by acetylcholine was significantly attenuated by Hcy in human IMA. Co‐incubation with AVE3085 protected endothelium from the impairment of Hcy. Exposure to Hcy for 24 h downregulated eNOS protein expression (P<0.05) whereas it upregulated the expression of eNOS at the mRNA level (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. Conclusions Hcy caused endothelial dysfunction through the modulation of NO production associated with a downregulation of eNOS in human IMA. AVE3085 prevents endothelial dysfunction, which is attributed to upregulation of eNOS expression. These findings provide new insights into the protection of the endothelium of the coronary artery bypass grafting conduits and the possible improvement of the long‐term patency of the grafts. Therefore, the present study may have strong clinical implications regarding the long‐term results of coronary artery surgery. Supported by National Natural Science Foundation of China (81641017), Zhejiang Provincial Natural Science Foundation (LY15H020008), Hangzhou Science and Technology Projects (20140633B12), & Tianjin Binhai Key Platform for Creative Research Program (2012‐BH110004), Binhai New Area Health Bureau (2016BWKZ003, 2016BWKY007, 2012BWKZ008) Support or Funding Information This study was supported by National Natural Science Foundation of China (81641017), Zhejiang Provincial Natural Science Foundation (LY15H020008), Hangzhou Science and Technology Projects (20140633B12), & Tianjin Binhai Key Platform for Creative Research Program (2012‐BH110004), Binhai New Area Health Bureau (2016BWKZ003, 2016BWKY007, 2012BWKZ008)