Dataset Information

HDL proteomics on CPROBE samples

ABSTRACT: Patients with chronic kidney disease (CKD) are at high risk for cardiovascular disease (CVD). However, traditional lipid risk factors, including low HDL levels, cannot completely explain the increased risk. Altered HDL proteome is linked with both CVD and CKD, but the role of HDL proteins in incident CVD events in CKD is unknown. In this prospective case-control study, we used targeted proteomics to quantify 31 proteins in HDL from 92 subjects (46 incident new CVD and 46 one-to-one matched controls) at various stages of CKD. We tested associations of HDL proteins with incident CVD using matched logistic regression analysis. In unadjusted models, levels of six HDL proteins (APOA1, APOA4, APOC3, LCAT, PON1, and PON3) significantly associated with incident CVD. No significant associations were found for HDL-C. In the fully adjusted model for clinical confounders and lipid levels, we observed an inverse association between levels of PON1, PON3, and LCAT in HDL and incident CVD. Odds ratios (per 1-SD) were 0.38 (0.18-0.97, P=0.042), 0.42 (0.20-0.92, P=0.031), and 0.30 (0.11-0.83, P=0.020) for PON1, PON3, and LCAT, respectively. APOA4 remained associated with incident CVD in CKD patients in models adjusted for clinical confounders and lipid levels but lost significance with the addition of CRP and proteinuria in the model. In conclusion, levels of four HDL proteins, PON1, PON3, LCAT, and APOA4, were inversely associated with incident CVD events in CKD subjects. Our observations indicate that HDL’s protein cargo but not HDL-C levels can serve as a marker—and perhaps mediator—for elevated CVD risk in CKD patients.

ORGANISM(S): Homo Sapiens

SUBMITTER: Baohai Shao

PROVIDER: PXD028216 | panorama | Sat Oct 23 00:00:00 BST 2021

REPOSITORIES: PanoramaPublic

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Publications

Altered HDL proteome predicts incident CVD in chronic kidney disease patients.

Shao Baohai B Mathew Anna V AV Thornock Carissa C Pennathur Subramaniam S

Journal of lipid research 20211009

Patients with chronic kidney disease (CKD) are at high risk for CVD. However, traditional lipid risk factors, including low HDL levels, cannot completely explain the increased risk. Altered HDL proteome is linked with both CVD and CKD, but the role of HDL proteins in incident CVD events in patients with CKD is unknown. In this prospective case-control study, we used targeted proteomics to quantify 31 HDL proteins in 92 subjects (46 incident new CVD and 46 one-to-one matched controls) at various ...[more]

PMID: 34634315

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Project description:Rationale: Epicardial adipose tissue (EAT) has been independently associated with non-calcified, high-risk coronary plaques in low-to intermediate risk subjects. Recently, a bidirectional communication was shown between EAT and diseased coronary arteries. In high-risk patients it is unknown whether quantitative measures of EAT can capture, and which molecular players are involved in this mutual interplay. Objective: In a high-risk population, we aimed to determine how the volume of EAT is linked to coronary artery disease (CAD) and to identify potential EAT-deregulated pathways in CAD patients specifically related to coronary artery calcification (CAC). Methods and Results: In a prospective cohort of 574 degenerative severe aortic stenosis patients referred to cardiac surgery, we quantified fat depots by computed tomography (CT) and performed a comparative quantitative proteomics of thoracic fat, including EAT, mediastinal (MAT) and subcutaneous (SAT) adipose tissues. We did not find an independent association of EAT volume with the severity, distribution and complexity of coronary stenosis in invasive coronary angiography. Although, EAT volume was correlated with high CAC, its cardiovascular risk factors-adjusted association was not significant. Taking as reference non-CAD matched-patients and compared to MAT and SAT, EAT proteomic signature of CAD was characterized by up-regulation of pro-calcifying annexins (Annexin A2, ANXA2), fatty acid binding transporters (FABP4) and inflammatory signaling proteins, and by down-regulation of fetuin-A and redox state regulatory enzymes. In EAT, ANXA2 regulation was positively correlated with CAC. EAT gene expression studies confirmed overexpression of ANXA2 and FABP4 in CAD, but no expression of FETUA was detected. Compared with non-CAD, fetuin-A circulating levels were higher in CAD, whereas no fetuin-A pericardial fluid differences were found. Conclusions: In this high-risk cohort, EAT presented an imbalance of pro-calcifying, pro-inflammatory and lipid transporters mediators. These local EAT-mediated regulatory mechanisms were not reflected by the CT volume of EAT alone.

Dataset Information

HDL proteomics on CPROBE samples

Publications

Altered HDL proteome predicts incident CVD in chronic kidney disease patients.

Similar Datasets

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