Dataset Information

HDL Proteomics in Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study

ABSTRACT: Atherosclerotic cardiovascular disease (CVD) is the major cause of death in patients with type 1 diabetes mellitus (T1DM). Alterations in the HDL proteome associate with prevalent CVD in T1DM. We therefore determined which proteins carried by HDL might predict incident CVD in T1DM patients. Using targeted MS/MS, we quantified 50 proteins in HDL from 181 T1DM subjects enrolled in the prospective Coronary Artery Calcification in Type 1 Diabetes study (CACTI). We used Cox proportional regression analysis and a case-cohort design to test associations of HDL proteins with incident CVD (myocardial infarction, coronary artery bypass grafting, angioplasty, or death from coronary heart disease). Only one HDL protein—SFTPB (pulmonary surfactant protein B)—predicted incident CVD in all of the models tested. In a fully adjusted model that controlled for lipids and other risk factors, the hazard ratio was 2.17 per SD increase of SFTPB (95% confidence interval, 1.12-4.21, P=0.022). Plasma fractionation demonstrated that plasma SFTPB is nearly quantitatively bound to HDL. Although previous studies have shown that high plasma levels of SFTPB associate with prevalent atherosclerosis only in smokers, we found that SFTPB predicted incident CVD in T1DM independently of smoking status. Elevated levels of SFTPB in HDL strongly predicted incident CVD in CACTI subjects independently of a wide range of confounding factors, including smoking status, HDL-C, LDL-C, and triglyceride levels. Because SFTPB is almost quantitatively bound to plasma HDL, our observations support the proposal that SFTPB carried by HDL is a marker—and perhaps mediator—of CVD risk in patients with T1DM.

ORGANISM(S): Homo Sapiens

SUBMITTER: Baohai Shao

PROVIDER: PXD031854 | panorama | Tue Apr 19 00:00:00 BST 2022

REPOSITORIES: PanoramaPublic

ACCESS DATA

Publications

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

Shao Baohai B Snell-Bergeon Janet K JK Pyle Laura L LL Thomas Katie E KE de Boer Ian H IH Kothari Vishal V Segrest Jere J Davidson William S WS Bornfeldt Karin E KE Heinecke Jay W JW

Journal of lipid research 20220314 4

Atherosclerotic CVD is the major cause of death in patients with type 1 diabetes mellitus (T1DM). Alterations in the HDL proteome have been shown to associate with prevalent CVD in T1DM. We therefore sought to determine which proteins carried by HDL might predict incident CVD in patients with T1DM. Using targeted MS/MS, we quantified 50 proteins in HDL from 181 T1DM subjects enrolled in the prospective Coronary Artery Calcification in Type 1 Diabetes study. We used Cox proportional regression an ...[more]

PMID: 35300983

Similar Datasets

Project description:This study was undertaken to test the hypothesis that short term exposure (4 hours) to physiologic hyperinsulinemia in normal, healthy subjects without a family history of diabetes would induce a low grade inflammatory response, independently of glycemic status. We performed euglycemic hyperinsulinemic (80 mU/m2/min) clamps in 12 healthy, insulin sensitive subjects with no family history of diabetes followed by biopsies of the vastus lateralis muscle taken basally and after 30 and 240 minutes of insulin infusion. Gene expression profiles were generated using Affymetrix HG-U133A arrays. No probe sets had significantly altered expression at 30 minutes of the insulin clamp, but 121 probe sets (117 upregulated and 4 downregulated) were significantly altered after 240 minutes. Hyperinsulinemia in normal, healthy human subjects increased the mRNAs for a number of inflammatory genes and transcription factors. Microarray and quantitative RT-PCR revealed the upregulation of chemokine, cc motif, ligand 2 (CCL2), CCL8, thrombomodulin (THBD), ras-related associated with diabetes (RRAD), metallothionein (MT), and serum/glucocorticoid regulated kinase (SGK), and downregulation of CITED2 (a CREB-binding protein-interacting transactivator), a known coactivator of PPAR-alpha. Interestingly, SGK and CITED2 are located at chromosome 6q23, where we previously detected strong linkage to hyperinsulinemia. A control saline infusion performed on 3 normal, healthy subjects without a family history of diabetes demonstrated that the genes altered following the euglycemic-hyperinsulinemic clamp were due to insulin and independent of biopsy removal. This study demonstrates that insulin acutely regulates the expression of genes involved in inflammation and transcription, and identifies several candidate genes/pathways for further investigation. Experiment Overall Design: Twelve subjects received a vastus lateralis muscle biopsy followed by a 180-min euglycemic, hyperinsulinemic (80 mU/m2.min) clamp. Muscle biopsies from each subject were homogenized in RNAStat solution (Tel-Test Inc., Friendswood, TX), using a Polytron homogenizer (Brinkmann Instruments Westbury, NY). Total RNA was purified with RNeasy and DNase I treatment (Qiagen, Chatsworth, CA). RNA was prepared for hybridization to Affymetrix (Santa Clara, CA) HG-U133A arrays according to the manufacturerâs instructions.

Dataset Information

HDL Proteomics in Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets