PXD002633

PXD002633 is an original dataset announced via ProteomeXchange.

Title	Effect of Rosuvastatin on the Lipoprotein Proteome
Description	Statins lower plasma cholesterol by as much as 50%, thus reducing future cardiovascular events. However, the physiological effects of statins are diverse and not all are related to LDL-C lowering. We performed a small clinical pilot study to assess the impact of statins on lipoprotein-associated proteins in healthy individuals (n=10) with normal LDL-C (<130 mg/dL), who were treated with rosuvastatin (20 mg/day) for 28 days. Proteomic analysis of size-exclusion chromatography isolated LDL, HDL-L (large) and HDL-S (small) fractions and spectral counting was used to compare relative protein detection before and after statin therapy. Significant protein changes were found in each lipoprotein pool and included both increases and decreases in several proteins involved in lipoprotein metabolism, complement regulation and acute phase response. The most dramatic effect of the rosuvastatin treatment was an increase in alpha-1-antirypsin (A1AT) spectral counts associated with HDL-L particles. Quantitative measurement by ELISA confirmed an average 5.7-fold increase in HDL-L associated A1AT. Molecular modeling predictions indicated that the hydrophobic reactive center loop of A1AT, the functional domain responsible for its protease inhibitor activity, is likely involved in its lipid binding and its association with HDL was found to protect A1AT against oxidative inactivation. Cell culture experiments, using J774 macrophages, demonstrated that the association of A1AT with HDL enhances its anti-protease activity, preventing elastase induced production of tumor necrosis factor alpha. In conclusion, we show that statins can significantly alter the protein composition of both LDL and HDL and our studies reveal a novel functional relationship between A1AT and HDL. The upregulation of A1AT on HDL enhances its anti-inflammatory functionality, which may contribute to the non-lipid lowering beneficial effects of statins.
HostingRepository	PRIDE
AnnounceDate	2018-10-24
AnnouncementXML	Submission_2018-10-24_08:12:43.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD002633
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Scott Gordon
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Deamidated; Oxidation; Carbamidomethyl
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2015-07-29 23:51:46	ID requested
⏵ 1	2018-10-24 08:12:45	announced

Gordon SM, McKenzie B, Kemeh G, Sampson M, Perl S, Young NS, Fessler MB, Remaley AT, Rosuvastatin Alters the Proteome of High Density Lipoproteins: Generation of alpha-1-antitrypsin Enriched Particles with Anti-inflammatory Properties. Mol Cell Proteomics, 14(12):3247-57(2015) [pubmed]

curator keyword: Biomedical

submitter keyword: Rosuvastatin, statin, lipoprotein, HDL, LDL

Scott M. Gordon
contact affiliation	National Heart, Lung, and Blood Institute, Lipoprotein Metabolism Section
contact email	scott.gordon@nih.gov
lab head
Scott Gordon
contact affiliation	National Institutes of Health
contact email	scott.gordon@nih.gov
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002633
     1. Label: PRIDE project
     2. Name: Effect of Rosuvastatin on the Lipoprotein Proteome