Open AccessCyanate‐Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion
Author(s) -
Sun Jia Teng,
Yang Ke,
Mao Jing Yan,
Shen Wei Feng,
Lu Lin,
Wu Qi Hong,
Wang Yan Ping,
Wu Li Ping,
Zhang Rui Yan
Publication year - 2016
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.116.004700
Subject(s) - medicine , cardiology , angiogenesis , collateral circulation , angina , stable angina , coronary occlusion , occlusion , coronary artery disease , myocardial infarction
Background Cyanate has recently gained attention for its role in the pathogenesis of vascular injury. Nonetheless, the effect of cyanate on angiogenesis remains unclear. Methods and Results In 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. Conclusions Impaired angiogenesis induced by cyanate might contribute to poor coronary collateral growth.