Proteomic Characterization of High-Density Lipoprotein Particles from Non-Diabetic Hemodialysis Patients
Nans Florens1,2, Catherine Calzada1, Frédéric Delolme3
1Univ. Lyon, CarMeN, INSERM U1060, INSA de Lyon, Université Claude Bernard Lyon 1, INRA U1397, F-69621 Villeurbanne, France.
Insights
High-density lipoprotein (HDL) protein changes in hemodialysis patients may explain HDL dysfunction and increased cardiovascular risk in chronic kidney disease (CKD). This study identified 19 altered HDL proteins in CKD patients undergoing hemodialysis.
Area of Science:
- Proteomics
- Cardiovascular Research
- Nephrology
Background:
- Chronic kidney disease (CKD) is linked to heightened cardiovascular disease (CVD) risk.
- Altered high-density lipoprotein (HDL) functionality is implicated in CKD-associated cardiovascular events.
Purpose of the Study:
- To characterize the HDL proteome in non-diabetic hemodialysis (HD) patients.
- To identify biological pathways affected by dysregulated HDL protein expression in CKD.
Main Methods:
- Proteomic analysis of HDL samples from 9 HD patients and 8 controls using nano-RSLC and Q-Orbitrap.
- Label-free quantification and database searching (SequestHT) for protein identification.
- Statistical analysis (pairwise ratios, ANOVA) to identify differentially expressed proteins (p < 0.05).
Main Results:
- Identified 326 proteins within the HDL proteome of HD and control patients.
- Found 10 significantly upregulated and 9 downregulated proteins in HD patients compared to controls.
- Dysregulated proteins were associated with lipid metabolism, hemostasis, wound healing, oxidative stress, and apoptosis.
Conclusions:
- The altered HDL proteome in HD patients suggests potential mechanisms for HDL dysfunction in CKD.
- These proteomic changes may contribute to the elevated cardiovascular risk observed in the CKD population.
Abstract:
Chronic kidney disease is associated with an increased cardiovascular risk, and altered biological properties of high-density lipoproteins (HDL) may play a role in these events. This study aimed to describe the HDL proteome from non-diabetic hemodialysis patients and identify potential pathways affected by the dysregulated expression of HDL proteins. HDL were sampled from nine non-diabetic hemodialysis (HD) and eight control patients. Samples were analyzed using a nano-RSLC coupled with a Q-Orbitrap. Data were processed by database searching using SequestHT against a human Swissprot database and quantified with a label-free quantification approach. Proteins that were in at least five of the eight control and six of the nine HD patients were analyzed. Analysis was based on pairwise ratios and the ANOVA hypothesis test. Among 522 potential proteins, 326 proteins were identified to be in the HDL proteome from HD and control patients, among which 10 were significantly upregulated and nine downregulated in HD patients compared to the control patients (p < 0.05). Up and downregulated proteins were involved in lipid metabolism, hemostasis, wound healing, oxidative stress, and apoptosis pathways. This difference in composition could partly explain HDL dysfunction in the chronic kidney disease (CKD) population and participate in the higher cardiovascular risk observed in this population.
