Summary of Study ST000659

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000463. The data can be accessed directly via it's Project DOI: 10.21228/M86P5J This work is supported by NIH grant, U2C- DK119886.

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Study IDST000659
Study TitleChanges in metabolites and lipid mediators associated with supervised exercise training for peripheral
Study TypeTimecourse
Study SummaryPeripheral artery disease (PAD) is a leading cause of cardiovascular related morbidity and mortality, affecting over 8.5 million men and women in the United States and greater than 200 million individuals worldwide. The mainstay of treatment to improve lower limb symptoms is supervised walking therapy, which does not affect plaque morphology or alter conduit artery blood flow, but rather ameliorates endothelial dysfunction, enhances skeletal muscle metabolism and mitochondrial function, and suppresses inflammatory activation. In this pilot feasibility project we will employ metabolic and lipidomic techniques to measure the effects of supervised exercise therapy on primary metabolism, complex lipids, and lipid mediators, and correlate these effects with individual, subject-level measures of the response to exercise therapy among subjects with PAD. The overarching theme of this work is to identify metabolites, complex lipids, and lipid mediators that are associated with the inter-individual variability in the response of subjects with PAD to supervised exercise therapy. This knowledge will significantly enhance our understanding of the pathophysiology of lower extremity symptoms in PAD, as well as the manner in which supervised exercise therapy improves walking intolerance. It will identify novel therapeutic targets and pathways for pharmacologic manipulation in the treatment of PAD. Aside from having the potential to generate multiple high-impact publications, it will serve as the basis for a planned NIH R01 submission by the PI at the conclusion of the award period.
Institute
University of California, Davis
DepartmentUSDA Western Human Nutrition Research Center
Last NameNewman
First NameJohn
Address430 West Health Sciences Dr. Davis, Ca, 95616
Emailjohn.newman@ars.usda.gov
Phone(530) 752-1009
Submit Date2017-06-28
Study CommentsFatty acids measured but not against a calibration curve. Therefore values are expressed as a relative abundance of the entire samples set such that the sum of all subjects eguals 100%.
Raw Data AvailableYes
Raw Data File Type(s)wiff
Analysis Type DetailLC-MS
Release Date2017-10-03
Release Version1
John Newman John Newman
https://dx.doi.org/10.21228/M86P5J
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000463
Project DOI:doi: 10.21228/M86P5J
Project Title:Changes in metabolites and lipid mediators associated with supervised exercise training for peripheral artery disease
Project Summary:Peripheral artery disease (PAD) is a leading cause of cardiovascular related morbidity and mortality, affecting over 8.5 million men and women in the United States and greater than 200 million individuals worldwide. The mainstay of treatment to improve lower limb symptoms is supervised walking therapy, which does not affect plaque morphology or alter conduit artery blood flow, but rather ameliorates endothelial dysfunction, enhances skeletal muscle metabolism and mitochondrial function, and suppresses inflammatory activation. In this pilot feasibility project we will employ metabolic and lipidomic techniques to measure the effects of supervised exercise therapy on primary metabolism, complex lipids, and lipid mediators, and correlate these effects with individual, subject-level measures of the response to exercise therapy among subjects with PAD. The overarching theme of this work is to identify metabolites, complex lipids, and lipid mediators that are associated with the inter-individual variability in the response of subjects with PAD to supervised exercise therapy. This knowledge will significantly enhance our understanding of the pathophysiology of lower extremity symptoms in PAD, as well as the manner in which supervised exercise therapy improves walking intolerance. It will identify novel therapeutic targets and pathways for pharmacologic manipulation in the treatment of PAD. Aside from having the potential to generate multiple high-impact publications, it will serve as the basis for a planned NIH R01 submission by the PI at the conclusion of the award period.
Institute:University of Pennsylvania
Department:Surgery, Perelman School of Medicine
Last Name:Damrauer
First Name:Scott
Address:3400 Spruce Street, 4 Silverstein Philadelphia, PA 19104
Email:Scott.Damrauer@uphs.upenn.edu
Phone:215-615-1698

Subject:

Subject ID:SU000682
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Gender:Male
Subject Comments:Individuals with peripheral arterial disease, as defined by ankle brachial indices ≥0.4 and ≤0.8 and the presence of classic claudication symptoms
Species Group:Human

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Visit Blood Draw
SA037819P1 H09v2 A
SA037820P1 D08v2 A
SA037821P1 G10v2 A
SA037822P1 A01v2 A
SA037823P1 E12v2 A
SA037824P1 H07v2 A
SA037825P1 E11v2 A
SA037826P1 D07v2 A
SA037827P1 A06v2 A
SA037828P1 F05v2 A
SA037829P1 C06v2 A
SA037830P1 H06v2 A
SA037831P2 C01v2 A
SA037832P1 A07v2 A
SA037833P1 F07v2 A
SA037834P2 F01v2 A
SA037835P2 B05v2 A
SA037836P2 A05v2 A
SA037837P2 G06v2 A
SA037838P2 C08v2 A
SA037839P2 D11v2 A
SA037840P2 H10v2 A
SA037841P2 F04v2 A
SA037842P2 C04v2 A
SA037843P2 G01v2 A
SA037844P1 D05v2 A
SA037845P2 G02v2 A
SA037846P2 H02v2 A
SA037847P2 G03v2 A
SA037848P2 F03v2 A
SA037849P2 E01v2 A
SA037850P1 A12v2 A
SA037851P1 A03v2 A
SA037852P1 H01v2 A
SA037853P1 H02v2 A
SA037854P1 H04v2 A
SA037855P1 F02v2 A
SA037856P1 C02v2 A
SA037857P1 C01v2 A
SA037858P1 H10v2 B
SA037859P1 A11v2 B
SA037860P1 C11v2 B
SA037861P2 E06v2 B
SA037862P1 A04v2 B
SA037863P1 E02v2 B
SA037864P2 F05v2 B
SA037865P2 D07v2 B
SA037866P2 F07v2 B
SA037867P1 F10v2 B
SA037868P2 C07v2 B
SA037869P2 A01v2 B
SA037870P1 G02v2 B
SA037871P2 D04v2 B
SA037872P2 B02v2 B
SA037873P2 A04v2 B
SA037874P1 A02v2 B
SA037875P1 G01v2 B
SA037876P2 E05v2 B
SA037877P1 G12v2 B
SA037878P1 H12v2 B
SA037879P2 G07v2 B
SA037880P1 C03v2 B
SA037881P2 E07v2 B
SA037882P1 F04v2 B
SA037883P2 B10v2 B
SA037884P2 H09v2 B
SA037885P2 C09v2 B
SA037886P2 D10v2 B
SA037887P1 B06v2 B
SA037888P1 B01v2 B
SA037889P1 H05v2 B
SA037890P1 B05v2 B
SA037891P2 F08v2 B
SA037892P2 D09v2 B
SA037893P2 A08v2 B
SA037894P1 B09v2 B
SA037895P1 F09v2 B
SA037896P1 G09v2 B
SA037897P1 F08v2 B
SA037898P1 G08v2 B
SA037899P2 B09v3 A
SA037900P1 B02v3 A
SA037901P2 A11v3 A
SA037902P2 B04v3 A
SA037903P2 G05v3 A
SA037904P2 H06v3 A
SA037905P1 D02v3 A
SA037906P2 C06v3 A
SA037907P2 G10v3 A
SA037908P2 F10v3 A
SA037909P2 A10v3 A
SA037910P2 B07v3 A
SA037911P2 F09v3 A
SA037912P2 E08v3 A
SA037913P2 F06v3 A
SA037914P1 E01v3 A
SA037915P2 C10v3 A
SA037916P2 H07v3 A
SA037917P2 D02v3 A
SA037918P1 A09v3 A
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Collection:

Collection ID:CO000676
Collection Summary:Blood was drawn form the subject at the baseline (Visit 2 (V2)) before (B) and after (A) the treadmill exercise test. Further, blood was collected after 12 weeks of supervised walking therapy (Visit 3 (V3)), before (B) and after (A) the treadmill exercise test.
Sample Type:Plasma

Treatment:

Treatment ID:TR000696
Treatment Summary:Subjects with peripheral arterial disease, as defined by ankle brachial indices ≥0.4 and ≤0.8 and the presence of classic claudication symptom were subjected to the treadmill exercise test. Further, they underwent 12 weeks of supervised walking therapy and subjected to the treadmill exercise test again.

Sample Preparation:

Sampleprep ID:SP000689
Sampleprep Summary:Lipid mediator extraction and quantification: Oxylipins, endocannabinoids, and fatty acids were isolated from plasma using Ostro Sample Preparation Plates (Waters; Milford, MA) in the presence of BHT/EDTA and quantified by UPLC-MS/MS using internal standard methods. Briefly, in the Ostro Plate well, 100µl plasma aliquots were mixed with 5µl of BHT/EDTA (1:1 v/v MeOH/water) and 5µl methanol containing a suite of deuterated surrogates. The samples were then mixed with 300µL of acetonitrile with 1% formic acid and eluted with 15 mmHg vacuum for 10 min into 200µL glass inserts containing 10µl of 20% glycerol in methanol. Solvent was removed by vacuum centrifugation and the glycerol plug was stored at -80Co until analysis. Prior acquisition, samples were reconstituted in 100µl of 1:1 methanol:acetonitrile containing 100nM of 1-cyclohexyl ureido, 3-dodecanoic acid (CUDA) and 1-phenyl ureido, 3-hexadecanoic acid (PUHA). Residues within extracts were separated on a 2.1 x 150mm 0.17µm BEH column (Waters) and detected by electrospray ionization with multi reaction monitoring on a API 6500 QTRAP (Sciex; Redwood City, CA) and quantified against 7-9 point calibration curves of authentic standards using modifications of previously reported methods (Grapov, D., et al. 2012. PLoS One 7: e48852.; doi: 10.1371/journal.pone.0048852).

Combined analysis:

Analysis ID AN001005 AN001006
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Waters Acquity Waters Acquity
Column Waters Acquity BEH C18 (100 x 2mm,1.7um) Waters Acquity BEH C18 (100 x 2mm,1.7um)
MS Type ESI ESI
MS instrument type Triple quadrupole Triple quadrupole
MS instrument name ABI Sciex 6500 QTrap ABI Sciex 6500 QTrap
Ion Mode POSITIVE NEGATIVE
Units Concentration pmol/g Concentration pmol/g

Chromatography:

Chromatography ID:CH000722
Methods Filename:2017_6500_OxyEndo_Analysis_protocol.pdf
Instrument Name:Waters Acquity
Column Name:Waters Acquity BEH C18 (100 x 2mm,1.7um)
Column Temperature:60 °C
Flow Gradient:See protocol/methods file
Flow Rate:0.25 uL
Internal Standard:See protocol/methods file
Retention Time:See protocol/methods file
Sample Injection:5 µL
Solvent A:100% water; 0.1% acetic acid
Solvent B:90% acetonitrile/ 10% isopropanol
Analytical Time:20 min
Weak Wash Solvent Name:20% methanol, 10% isopropanol
Weak Wash Volume:600 µL
Strong Wash Solvent Name:50:50 Acetonitrile:Methanol
Strong Wash Volume:600 µL
Chromatography Type:Reversed phase

MS:

MS ID:MS000900
Analysis ID:AN001005
Instrument Name:ABI Sciex 6500 QTrap
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:Endocannabinoid Analysis
Ion Mode:POSITIVE
  
MS ID:MS000901
Analysis ID:AN001006
Instrument Name:ABI Sciex 6500 QTrap
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:Oxylipin Analysis
Ion Mode:NEGATIVE
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