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

Abstract

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.

Effects of four different antihypertensive drugs on plasma metabolomic profiles in patients with essential hypertension

“…some of the deleterious effects of uremia [ 40 ]. Elevated plasma protein-bound homocitrulline concentrations predict increased risk of coronary artery disease, future myocardial infarction, stroke and death [ 39 ], and elevated free serum homocitrulline concentration is associated with poor coronary collateral growth in coronary heart disease patients [ 41 ]. However, it remains unclear whether reduction of homocitrulline levels by amlodipine (median change -21%, P = 9 x 10 −4 ) and elevation of its levels by hydrochlorothiazide (median change +16%, P = 0.004) have any relation to risk reduction of cardiovascular events during antihypertensive treatment.…”

Association of carbamylated high-density lipoprotein with coronary artery disease in type 2 diabetes mellitus: carbamylated high-density lipoprotein of patients promotes monocyte adhesion

“…Protein carbamylation is produced by interactions between cyanate and free amino groups, which preferentially occur on the e-NH2 of lysine residues and generate carbamyl-lysine (CBL), a characteristic carbamylation-derived product [ 11 ]. Cyanate, which is formed by myeloperoxidase-catalyzed oxidation of thiocyanate or by urea dissociation, is increased at inflammatory sites and in chronic kidney disease [ 12 , 13 ]. Thus, carbamylation can reflect the burden of enhanced inflammation, oxidative stress, and renal impairment, and can serve as a biomarker of certain pathological conditions [ 13 , 14 ].…”

Protein carbamylation in end stage renal disease

“…These findings remained significant following adjustment for traditional CV risks factors, GFR, and inflammatory markers. Others have shown similar results in smaller studies [31, 32]. Thus, it seems measures of systemic protein carbamylation burden can independently predict CV outcomes, and advanced kidney disease is not a pre-requisite.…”