PXD031854

PXD031854 is an original dataset announced via ProteomeXchange.

Title	HDL Proteomics in Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study
Description	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.
HostingRepository	PanoramaPublic
AnnounceDate	2022-04-19
AnnouncementXML	Submission_2022-04-19_20:26:10.094.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Baohai Shao
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	Carbamidomethyl; Label:13C(6)15N(4); Label:15N(1); Label:15N(2)
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-23 18:04:30	ID requested
⏵ 1	2022-04-19 20:26:11	announced

Shao B, Snell-Bergeon JK, Pyle LL, Thomas KE, de Boer IH, Kothari V, Segrest J, Davidson WS, Bornfeldt KE, Heinecke JW, Pulmonary surfactant protein B carried by HDL predicts incident CVD in patients with type 1 diabetes. J Lipid Res, 63(4):100196(2022) [pubmed]

submitter keyword: HDL proteomics, CACTI, Diabetes, incident CVD, parallel reaction monitoring, quantification, Orbitrap Fusion Lumos, Skyline

Baohai Shao
contact affiliation	University of Washington
contact email	bhshao@uw.edu
lab head
Baohai Shao
contact affiliation	University of Washington
contact email	bhshao@uw.edu
dataset submitter

Panorama Public dataset URI