Altered HDL proteome predicts incident CVD in chronic kidney disease patients

Shao, Baohai; Mathew, Anna V.; Thornock, Carissa; Pennathur, Subramaniam; Kretzler, Matthias; Gipson, Debbie S.; Bitzer, Markus; Gadegbeku, Crystal A.; Bellovich, Keith; Bhat, Zeenat; Massengill, Susan; Perumal, Kalyani

doi:10.1016/j.jlr.2021.100135

Cited by 20 publications

(19 citation statements)

References 55 publications

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“…We tested the hypothesis that the levels of one or more HDL proteins associate with incident CVD in subjects with T1DM. HDL was isolated from freshly thawed serum by ultracentrifugation, and its protein composition was quantified by isotope-dilution MS/MS with PRM ( 26 , 27 ). An unadjusted analysis revealed that 11 proteins were differentially expressed in HDL isolated from the control group and from the incident CVD group ( supplemental Table S2 ).…”

Section: Resultsmentioning

confidence: 99%

“…We used targeted proteomics with isotope-dilution parallel reaction monitoring (PRM) to quantify HDL proteins ( 26 , 27 ). Briefly, LC-ESI-MS/MS analyses were performed in the positive-ion mode with an ultrahigh-resolution accurate mass Orbitrap Fusion Lumos Tribrid mass spectrometer (Thermo Fisher Scientific, San Jose, CA) coupled to a nanoACQUITY UPLC (Waters, Milford, MA).…”

Section: Methodsmentioning

confidence: 99%

“…Results of our previous studies ( 16 , 27 , 28 ) and a preliminary shotgun analysis of HDL isolated from 40 CACTI subjects were used to select 50 HDL proteins for relative quantification. Initially, at least two peptides from one protein were tested by PRM test runs, and finally, two peptides were selected for 35 proteins and one peptide for 15 proteins for quantification ( supplemental Table S1 ).…”

Section: Methodsmentioning

confidence: 99%

“…Quantifying HDL proteins with 15 N-labeled APOA1. The relative levels of proteins in HDL were quantified by PRM with isotope dilution, using [ 15 N]APOA1 as the internal standard (27). The PRM data were analyzed with Skyline (version 21.1.0.278), an open source program (29).…”

Section: Liquid Chromatography-electrospray Ionization Tandem Mass Sp...mentioning

confidence: 99%

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Pulmonary surfactant protein B carried by HDL predicts incident CVD in patients with type 1 diabetes

Shao

Snell‐Bergeon

Pyle

et al. 2022

Journal of Lipid Research

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Liquid Chromatography-electrospray Ionization Tandem Mass Sp...mentioning

confidence: 99%

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Pulmonary surfactant protein B carried by HDL predicts incident CVD in patients with type 1 diabetes

Shao

Snell‐Bergeon

Pyle

et al. 2022

Journal of Lipid Research

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“…Untersteller et al showed that neither the quantity of HDL-C nor the composition or function of HDL-C could predict cardiovascular outcome among CKD patients independently ( 25 ). Shao et al found that the protein cargo of HDL-C could be used as a biomarker and mediator for elevated CVD risk in CKD patients ( 26 ). Calabresi et al reported that acquired plasma lecithin cholesterol acyltransferase (LCAT) deficiency was a major cause of low plasma HDL levels in patients with CKD, making it an attractive therapeutic target to reverse dyslipidaemia and reduce potential cardiovascular events ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

Using Machine Learning to Evaluate the Role of Microinflammation in Cardiovascular Events in Patients With Chronic Kidney Disease

et al. 2022

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BackgroundLipid metabolism disorder, as one major complication in patients with chronic kidney disease (CKD), is tied to an increased risk for cardiovascular disease (CVD). Traditional lipid-lowering statins have been found to have limited benefit for the final CVD outcome of CKD patients. Therefore, the purpose of this study was to investigate the effect of microinflammation on CVD in statin-treated CKD patients.MethodsWe retrospectively analysed statin-treated CKD patients from January 2013 to September 2020. Machine learning algorithms were employed to develop models of low-density lipoprotein (LDL) levels and CVD indices. A fivefold cross-validation method was employed against the problem of overfitting. The accuracy and area under the receiver operating characteristic (ROC) curve (AUC) were acquired for evaluation. The Gini impurity index of the predictors for the random forest (RF) model was ranked to perform an analysis of importance.ResultsThe RF algorithm performed best for both the LDL and CVD models, with accuracies of 82.27% and 74.15%, respectively, and is therefore the most suitable method for clinical data processing. The Gini impurity ranking of the LDL model revealed that hypersensitive C-reactive protein (hs-CRP) was highly relevant, whereas statin use and sex had the least important effects on the outcomes of both the LDL and CVD models. hs-CRP was the strongest predictor of CVD events.ConclusionMicroinflammation is closely associated with potential CVD events in CKD patients, suggesting that therapeutic strategies against microinflammation should be implemented to prevent CVD events in CKD patients treated by statin.

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Cholesterol transport and beyond: Illuminating the versatile functions of HDL apolipoproteins through structural insights and functional implications

Bhale,

Meilhac,

d'Hellencourt

et al. 2024

BioFactors

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High‐density lipoproteins (HDLs) play a vital role in lipid metabolism and cardiovascular health, as they are intricately involved in cholesterol transport and inflammation modulation. The proteome of HDL particles is indeed complex and distinct from other components in the bloodstream. Proteomics studies have identified nearly 285 different proteins associated with HDL; however, this review focuses more on the 15 or so traditionally named “apo” lipoproteins. Important lipid metabolizing enzymes closely working with the apolipoproteins are also discussed. Apolipoproteins stand out for their integral role in HDL stability, structure, function, and metabolism. The unique structure and functions of each apolipoprotein influence important processes such as inflammation regulation and lipid metabolism. These interactions also shape the stability and performance of HDL particles. HDLs apolipoproteins have multifaceted roles beyond cardiovascular diseases (CVDs) and are involved in various physiological processes and disease states. Therefore, a detailed exploration of these apolipoproteins can offer valuable insights into potential diagnostic markers and therapeutic targets. This comprehensive review article aims to provide an in‐depth understanding of HDL apolipoproteins, highlighting their distinct structures, functions, and contributions to various physiological processes. Exploiting this knowledge holds great potential for improving HDL function, enhancing cholesterol efflux, and modulating inflammatory processes, ultimately benefiting individuals by limiting the risks associated with CVDs and other inflammation‐based pathologies. Understanding the nature of all 15 apolipoproteins expands our knowledge of HDL metabolism, sheds light on their pathological implications, and paves the way for advancements in the diagnosis, prevention, and treatment of lipid and inflammatory‐related disorders.

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Altered HDL proteome predicts incident CVD in chronic kidney disease patients

Cited by 20 publications

References 55 publications

Pulmonary surfactant protein B carried by HDL predicts incident CVD in patients with type 1 diabetes

Pulmonary surfactant protein B carried by HDL predicts incident CVD in patients with type 1 diabetes

Using Machine Learning to Evaluate the Role of Microinflammation in Cardiovascular Events in Patients With Chronic Kidney Disease

Cholesterol transport and beyond: Illuminating the versatile functions of HDL apolipoproteins through structural insights and functional implications

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