# Serum YB-1 links dyslipidemia to NET-mediated vascular calcification in hemodialysis

## TL;DR

Serum YB-1 is a new predictor of vascular calcification in hemodialysis patients, linking dyslipidemia to neutrophil activity and heart disease risk.

## Contribution

Serum YB-1 is identified as a novel mechanistic and predictive biomarker linking dyslipidemia to vascular calcification in hemodialysis patients.

## Key findings

- Serum YB-1 levels are independently associated with new-onset vascular calcification in hemodialysis patients.
- YB-1 outperforms traditional lipid, glucose, and bone-based models in predicting vascular calcification.
- YB-1 enhances neutrophil lipid metabolism and NET formation, promoting vascular smooth muscle cell calcification.

## Abstract

Vascular calcification (VC) is highly prevalent in patients undergoing maintenance hemodialysis (MHD) and is associated with cardiovascular morbidity. However, traditional lipid and mineral markers have limited predictive value. Y-box binding protein-1 (YB-1), a regulator of lipid metabolism and inflammation, may provide additional mechanistic and clinical insight.

Serum YB-1 was measured in 209 MHD patients (30-month follow-up) who were stratified into hyperlipidemia and control groups. Receiver Operating Characteristic (ROC) and decision curve analysis (DCA, threshold range 0.1–0.4) were used to assess the predictive performance of YB-1 against traditional models based on lipid, glucose, and bone metabolism. Mechanistic studies in HL-60-derived neutrophil-like cells and a 5/6 nephrectomized rat model were performed to assess the role of YB-1 in neutrophil extracellular trap (NET) formation and VC.

Serum YB-1 was significantly elevated in hyperlipidemia patients and was independently associated with new-onset VC (AUC 0.707, 95% CI 0.630–0.784). YB-1 outperformed lipid-, glucose-, and bone-based models, providing added net clinical benefit in DCA within the 0.24–0.33 threshold range. Mechanistically, serum levels of citrullinated histone H3 (citH3), a NET marker, were increased in hyperlipidemia patients. In vitro, YB-1 and IS synergistically enhanced neutrophil lipid droplet accumulation and citH3 release, while NET-rich supernatants promoted VSMC calcification. In vivo, IS-treated 5/6 nephrectomy rats displayed elevated YB-1, increased citH3, and aggravated aortic calcification.

Serum YB-1 is a novel predictor and potential mechanistic mediator of VC in MHD patients. Incorporating YB-1 into existing clinical risk models may support earlier recognition of individuals at elevated cardiovascular risk and inform more effective management strategies to improve long-term health outcomes.

The online version contains supplementary material available at 10.1186/s12944-025-02832-y.

Extracellular YB-1 reprograms neutrophil lipid metabolism to enhance NET formation and drive VSMC calcification under uremic conditions.

Clinically, serum YB-1 levels are independently associated with dyslipidemia in MHD patients.

YB-1 acts as a mechanistic bridge linking dyslipidemia to vascular calcification in MHD patients.

Integrating YB-1 improves vascular calcification prediction beyond traditional metabolic markers, providing measurable net clinical benefit in intermediate-risk MHD patients.

The online version contains supplementary material available at 10.1186/s12944-025-02832-y.