Cyanate‐Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion

BackgroundCyanate has recently gained attention for its role in the pathogenesis of vascular injury. Nonetheless, the effect of cyanate on angiogenesis remains unclear. Methods and ResultsIn this study, we demonstrated that oral administration of cyanate impaired blood perfusion recovery in a mouse...

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Main Authors: Jia Teng Sun, Ke Yang, Jing Yan Mao, Wei Feng Shen, Lin Lu, Qi Hong Wu, Yan Ping Wang, Li Ping Wu, Rui Yan Zhang
Format: Article
Language:English
Published: Wiley 2016-12-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Subjects:
Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.116.004700
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author Jia Teng Sun
Ke Yang
Jing Yan Mao
Wei Feng Shen
Lin Lu
Qi Hong Wu
Yan Ping Wang
Li Ping Wu
Rui Yan Zhang
author_facet Jia Teng Sun
Ke Yang
Jing Yan Mao
Wei Feng Shen
Lin Lu
Qi Hong Wu
Yan Ping Wang
Li Ping Wu
Rui Yan Zhang
author_sort Jia Teng Sun
collection DOAJ
description BackgroundCyanate has recently gained attention for its role in the pathogenesis of vascular injury. Nonetheless, the effect of cyanate on angiogenesis remains unclear. Methods and ResultsIn this study, we demonstrated that oral administration of cyanate impaired blood perfusion recovery in a mouse hind‐limb ischemia model. A reduction in blood perfusion recovery at day 21 was observed in the ischemic tissue of cyanate‐treated mice. Likewise, there were fewer capillaries in the ischemic hind‐limb tissue of cyanate‐exposed mice. Our in vitro study showed that cyanate, together with its carbamylated products, inhibited the migration, proliferation, and tube‐formation abilities of endothelial cells. Further research revealed that cyanate regulated angiogenesis partly by interrupting the vascular endothelial growth factor receptor 2/phosphatidylinositol 3‐kinase/Akt pathway. The serum concentrations of homocitrulline, a marker of cyanate exposure, were determined in 117 patients with stable angina and chronic total occlusion. Consistent with the antiangiogenic role of cyanate, homocitrulline levels were increased in patients with poor coronary collateralization (n=58) compared with those with high collateralization (n=59; 21.09±13.08 versus 15.54±9.02 ng/mL, P=0.009). In addition, elevated homocitrulline concentration was a strong predictor of poor coronary collateral growth. ConclusionsImpaired angiogenesis induced by cyanate might contribute to poor coronary collateral growth.
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spelling doaj.art-c08b0b97018746f088222dcc952d75a12022-12-21T23:53:09ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802016-12-0151210.1161/JAHA.116.004700Cyanate‐Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total OcclusionJia Teng Sun0Ke Yang1Jing Yan Mao2Wei Feng Shen3Lin Lu4Qi Hong Wu5Yan Ping Wang6Li Ping Wu7Rui Yan Zhang8Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaInstitute of Cardiovascular Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaInstitute of Neuroscience, Chinese Academy of Sciences, Shanghai, ChinaDepartment of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaInstitute of Cardiovascular Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaInstitute of Cardiovascular Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaBackgroundCyanate has recently gained attention for its role in the pathogenesis of vascular injury. Nonetheless, the effect of cyanate on angiogenesis remains unclear. Methods and ResultsIn this study, we demonstrated that oral administration of cyanate impaired blood perfusion recovery in a mouse hind‐limb ischemia model. A reduction in blood perfusion recovery at day 21 was observed in the ischemic tissue of cyanate‐treated mice. Likewise, there were fewer capillaries in the ischemic hind‐limb tissue of cyanate‐exposed mice. Our in vitro study showed that cyanate, together with its carbamylated products, inhibited the migration, proliferation, and tube‐formation abilities of endothelial cells. Further research revealed that cyanate regulated angiogenesis partly by interrupting the vascular endothelial growth factor receptor 2/phosphatidylinositol 3‐kinase/Akt pathway. The serum concentrations of homocitrulline, a marker of cyanate exposure, were determined in 117 patients with stable angina and chronic total occlusion. Consistent with the antiangiogenic role of cyanate, homocitrulline levels were increased in patients with poor coronary collateralization (n=58) compared with those with high collateralization (n=59; 21.09±13.08 versus 15.54±9.02 ng/mL, P=0.009). In addition, elevated homocitrulline concentration was a strong predictor of poor coronary collateral growth. ConclusionsImpaired angiogenesis induced by cyanate might contribute to poor coronary collateral growth.https://www.ahajournals.org/doi/10.1161/JAHA.116.004700angiogenesiscarbamylationchronic total coronary occlusioncollateral circulationcyanateendothelial dysfunction
spellingShingle Jia Teng Sun
Ke Yang
Jing Yan Mao
Wei Feng Shen
Lin Lu
Qi Hong Wu
Yan Ping Wang
Li Ping Wu
Rui Yan Zhang
Cyanate‐Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
angiogenesis
carbamylation
chronic total coronary occlusion
collateral circulation
cyanate
endothelial dysfunction
title Cyanate‐Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion
title_full Cyanate‐Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion
title_fullStr Cyanate‐Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion
title_full_unstemmed Cyanate‐Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion
title_short Cyanate‐Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion
title_sort cyanate impaired angiogenesis association with poor coronary collateral growth in patients with stable angina and chronic total occlusion
topic angiogenesis
carbamylation
chronic total coronary occlusion
collateral circulation
cyanate
endothelial dysfunction
url https://www.ahajournals.org/doi/10.1161/JAHA.116.004700
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