Cold shock Y-box binding protein-1 acetylation status in monocytes is associated with systemic inflammation and vascular damage.

Abstract Background and aims In dialysis patients, vascular morbidities are highly prevalent and linked to leukocyte extravasation, especially of polarized monocytes. Experimental data demonstrate that phenotypic changes in monocytes require Y-box binding protein-1 (YB-1) upregulation. Methods We determined YB-1 expression in circulating and vessel-invading monocytes from healthy controls and dialysis patients to correlate results with intima plaque formation and systemic inflammation. Results Compared to healthy subjects, dialysis patients have fewer classical and more intermediate and non-classical monocytes. Post-translationally modified YB-1 (lysine 301/304 acetylation) is detected at high levels in the nucleus of adherent and invading CD14+CD68+ monocytes from umbilical cord and atherosclerosis-prone vessels. The content of non-acetylated YB-1 is significantly decreased (p < 0.001), whereas acetylated YB-1 is correspondingly increased (p < 0.001) throughout all monocyte subpopulations, such that the overall content remains unchanged. Conclusions In dialysis patients the YB-1 acetylation status is higher with prevailing diabetes and intima plaque formation. Pro-inflammatory mediators TNFα, IL-6, uPAR, CCL2, M-CSF, progranulin, ANP, and midkine, as well as anti-inflammatory IL-10 are significantly increased in dialysis patients, emphasizing a systemic inflammatory milieu. Strong positive correlations of monocytic YB-1 content are seen with ANP, IP-10, IL-6, and IL-10 serum levels. This is the first study demonstrating an association of cold shock protein YB-1 expression with inflammation in hemodialysis patients. Highlights • In hemodialysis (HD) patients the level of acetylated YB-1 is increased (p < 0.001) in all monocytic subpopulations. • In HD patients with vascular damage (intima plaques, increased intima media thickness) alterations of monocytic YB-1 content are apparent. • Serum cytokine levels show a close correlation between monocytic YB-1 content and systemic inflammatory status. • The correlation of monocytic YB-1 content with disease and systemic inflammation suggests a causal link. [ABSTRACT FROM AUTHOR]