Kynurenine pathway - a new link between endothelial dysfunction and carotid atherosclerosis in chronic kidney disease patients.
OBJECTIVE
The endothelium dysfunction is an important component of atherosclertic cardiovascular disease. It has been also suggested that kynurenine pathway activation may be involved in the pathogenesis of this disease.


METHODS
This is a cross-sectional study in chronic kidney disease (CKD) patients (n=106; 60 Males). The plasma markers of endothelial dysfunction and kynurenine (KYN), 3-hydroxykynurenine (3-HKYN), kynurenic acid (KYNA), anthranilic acid (AA) and quinolinic acid (QA) were measured in relation to an early indicator of the systemic atherosclerosis - intima-media thickness (IMT).


RESULTS
Kynurenines, von Willebrand factor (vWF), thrombomodulin (TM), soluble adhesion molecules (sICAM-1, sVCAM-1) and IMT in each uraemic group were significantly higher than in healthy people. In contrast, no significant differences in sE-selectin and sP-selectin concentrations were observed between CKD patients and controls. Kynurenines were positively associated with vWF, TM, sICAM-1 and sVCAM-1, whereas sP-selectin was inversely associated with the most of kynurenines. IMT was positively correlated both with kynurenines: KYN, 3-HKYN, QA as well as with endothelial markers: TM, vWF, sICAM-1 and sVCAM-1 (all p<0.01). Finally, multiple regression analysis identified age, vWF, sVCAM-1 and QA levels as the independent variables significantly associated with increased IMT in this population (adjusted r² = 0.51).


CONCLUSIONS
This study suggests a relationship between kynurenine pathway activation, endothelial dysfunction and the progression of atherosclerosis in CKD patients. It opens a new idea that the inhibition of kynurenine pathway may provide an effective strategy to slow down endothelial dysfunction and thereby the prevalence of atherosclerosis in this population.
Pawlak
K
K
Department of Monitored Pharmacotherapy, Medical University, Bialystok, Poland.
Myśliwiec
M
M
Pawlak
D
D
D000328:Adult; D002340:Carotid Artery Diseases / Q000097:blood* / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000378:metabolism*; D007737:Kynurenine / Q000097:blood* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology*; D018180:Thrombomodulin / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism
D015815:Cell Adhesion Molecules; D018180:Thrombomodulin; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D007737:Kynurenine