PXD057196-1

PXD057196 is an original dataset announced via ProteomeXchange.

Title	ApoA-I [human] (CSL112) infusion increases LCAT levels in HDL particles and promotes reverse cholesterol transport
Description	Background: High-density lipoprotein (HDL)-cholesterol is inversely correlated with cardiovascular risk, but increasing its circulating concentration is insufficient to prevent adverse cardiovascular outcomes. Instead, the emerging paradigm is on increasing the function of HDL and its major protein constituent, apolipoprotein A-I (apoA-I) to increase reverse cholesterol transport. Objective: To investigate the effect of apoA-I [human] (CSL112) infusion on HDL protein composition, and provide further insights into the mechanism of action of CSL112 administered post-acute myocardial infarction (AMI). Methods: A mass spectrometry (MS)-based proteomic approach was used to evaluate changes in HDL protein composition in patients (n=50) from the AEGIS-I (ApoA-I Event Reducing in Ischemic Syndromes I) study who received either placebo or CSL112 post-AMI. HDL was immuno-isolated from patient plasma using anti-apoA-I antibodies. Cholesterol esterification rate (CER) was measured to determine lecithin-cholesterol acyl transferase (LCAT) activity. Cholesterol efflux capacity (CEC) and hepatocyte uptake were assessed using patient serum in ex vivo cell-based assays. Results: CSL112 induced extensive rearrangement of HDL proteins at 4 hours post-infusion. Levels of apolipoproteins A2, B, C, and E, as well as the acute phase proteins serum amyloid A1 and A4 were significantly reduced. By contrast, apoA-I, apoM, and LCAT significantly increased. Elevated apoA-I and LCAT levels on HDL were associated with an increase in CEC, plasma HDL-C levels, and CER in CSL112-treated patients. Furthermore, enhanced CEC was strongly associated with cholesterol uptake by hepatic cells (r=0.95 p<0.001). Conclusions: CSL112 altered HDL composition and increased HDL functionality by promoting multiple steps of the reverse cholesterol transport pathway. Clinical trial registration: URL: https://clinicaltrials.gov. Unique identifier: NCT02108262
HostingRepository	PRIDE
AnnounceDate	2025-06-16
AnnouncementXML	Submission_2025-06-15_17:37:07.429.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD057196
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Rommel Mathias
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-25 06:35:07	ID requested
⏵ 1	2025-06-15 17:37:08	announced

Mathias RA, Velkoska E, Didichenko SA, Greene BH, Tan X, Navdaev AV, Collins HL, Adelman SJ, Young K, Gille A, Duffy D, Gibson CM, Pelzing M, Kingwell BA, and Promotes Reverse Cholesterol Transport. JACC Basic Transl Sci, 10(4):405-418(2025) [pubmed]

10.6019/PXD057196;

10.1016/j.jacbts.2024.11.001;

submitter keyword: lecithin-cholesterol acyl transferase, proteome,CSL112, high-density lipoprotein, acute myocardial infarction

Matthias Pelzing
contact affiliation	Analytical Biochemistry Global Research CSL
contact email	matthias.pelzing@csl.com.au
lab head
Rommel Mathias
contact affiliation	CSL
contact email	rommel.mathias@csl.com.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD057196
     1. Label: PRIDE project
     2. Name: ApoA-I [human] (CSL112) infusion increases LCAT levels in HDL particles and promotes reverse cholesterol transport