PXD003980

PXD003980 is an original dataset announced via ProteomeXchange.

Title	Integrated Omic Analysis of a Guinea Pig Model of Heart Failure and Sudden Cardiac Death
Description	Here we examine key regulatory pathways underlying the transition from compensated hypertrophy (HYP) to decompensated heart failure (HF) and sudden cardiac death (SCD) in a guinea pig model by integrated multi-ome analysis. Relative protein abundances from sham-operated, HYP and HF hearts were assessed by iTRAQ shotgun LC-MS/MS. Metabolites were quantified by LC-MS/MS or GC-MS. Transcriptome profiles were obtained using DNA microarrays. The guinea pig HF proteome exhibited classic biosignatures of cardiac HYP, left ventricular dysfunction, fibrosis, inflammation and extravasation. Fatty acid metabolism, mitochondrial transcription/translation factors, antioxidant enzymes, and other mitochondrial processes, were downregulated in HF, but not HYP. Proteins upregulated in HF implicate extracellular matrix remodeling, cytoskeletal remodeling, and acute phase inflammation markers. Among metabolites, downregulation of acyl-carnitines was observed in HYP, while fatty acids accumulated in HF. Correlation of transcript and protein changes in HF is weak (R2=0.23), suggesting transcript/proteome divergence may reveal post-transcriptional gene regulation in HF. Proteome/Metabolome integration suggests metabolic bottlenecks in fatty acyl-CoA processing by carnitine palmitoyl transferase (CPT1B) as well as TCA cycle inhibition. We present a model by which acute signaling in HF, including Ca2+ dysregulation and low cAMP levels, is coupled to mitochondrial metabolic and antioxidant defects, through a CREB/PGC1 transcriptional axis. Animal Model The guinea pig model of heart failure and sudden cardiac death has been described previously. Briefly, the HF and SCD guinea pig model was produced by combining ascending aortic constriction (AC) and daily isoproterenol challenge (ACi model). Specifically, Hartley guinea pigs (~250 g; Hilltop Lab Animals) were anesthetized with 4% isoflurane in a closed box for 4min, and then intubated and ventilated with oxygen and 2% isoflurane. Ascending aortic constriction (AC) was produced by tying a suture around the ascending aorta using an 18‐gauge needle as a spacer, which was then removed. For sham operations the procedure was identical though the suture was not tied. After the procedure, bupronex (0.05 mg/kg) was administered via intramuscular injection for analgesia and animals were observed until full recovery. Isoproterenol was administered daily by intra peritoneal injection at 1 mg/kg for the first week after surgery and at 2 mg/kg for a subsequent 3 weeks. As characterized previously (1), cardiac function of ACi animal is well compensated in the first 2 weeks (HYP) but declined rapidly thereafter (HF). Hypertrophic heart was collected between 1-2 weeks post-surgery (ACi-2w), whereas failing heart was collected at 4 weeks after surgery (ACi-4w). Following retrograde perfusion with 20ml Tyrode’s solution, excised hearts were Snap-frozen in liquid N2 and stored at -80°C Experimental Design The experiment consisted of 3 treatment groups: 1) HYP (ACi-2wk), 2) HF (ACi-4wk) 3) sham-operated animals with daily administration for 4 weeks (Shami-4w). 1 heart from each group was included in an iTRAQ 4-plex experiment wherein peptides from each heart are subjected to reaction with an isobaric label. The experiment was repeated twice, yielding a total of 3 independent experiments quantifying the peptides from 9 hearts. ITRAQ reagents were shuffled among treatment groups for each experiment to minimize labeling bias.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_03:58:54.034.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	D. Brian Foster
SpeciesList	scientific name: Cavia porcellus (Guinea pig); NCBI TaxID: 10141;
ModificationList	iTRAQ4plex-116 reporter+balance reagent acylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2016-04-18 05:33:13	ID requested
1	2018-10-26 02:54:55	announced
⏵ 2	2024-10-22 03:58:55	announced	2024-10-22: Updated project metadata.

10.1021/acs.jproteome.6b00149;

Foster DB, Liu T, Kammers K, O'Meally R, Yang N, Papanicolaou KN, Talbot CC, Cole RN, O'Rourke B, Integrated Omic Analysis of a Guinea Pig Model of Heart Failure and Sudden Cardiac Death. J Proteome Res, 15(9):3009-28(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: Heart, proteomics, Cardiac, iTRAQ

D. Brian Foster
contact affiliation	Division of Cardiology Johns Hopkins University School of Medicine Ross Research Building, Room 847 720 Rutland Avenue Baltimore, MD 21205 Phone: 410-614-0027 Email: dbrianfoster@jhmi.edu Web: http://web1.johnshopkins.edu/fosterlab
contact email	dbrianfoster@jhmi.edu
lab head
D. Brian Foster
contact affiliation	Johns Hopkins University School of Medicine
contact email	dbrianfoster@jhmi.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/10/PXD003980

PRIDE project URI

• PRIDE
  1. PXD003980
     1. Label: PRIDE project
     2. Name: Integrated Omic Analysis of a Guinea Pig Model of Heart Failure and Sudden Cardiac Death