Proteomic analysis of coronary sinus serum reveals leucine-rich α2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure.

Hdl Handle:
http://hdl.handle.net/10147/129749
Title:
Proteomic analysis of coronary sinus serum reveals leucine-rich α2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure.
Authors:
Watson, Chris J; Ledwidge, Mark T; Phelan, Dermot; Collier, Patrick; Byrne, Jennifer C; Dunn, Michael J; McDonald, Kenneth M; Baugh, John A
Affiliation:
School of Medicine and Medical Science, St Vincent's University Hospital and The Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland.
Citation:
Proteomic analysis of coronary sinus serum reveals leucine-rich α2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure. 2011, 4 (2):188-97 Circ Heart Fail
Journal:
Circulation. Heart failure
Issue Date:
1-Mar-2011
URI:
http://hdl.handle.net/10147/129749
DOI:
10.1161/CIRCHEARTFAILURE.110.952200
PubMed ID:
21282491
Abstract:
Heart failure (HF) prevention strategies require biomarkers that identify disease manifestation. Increases in B-type natriuretic peptide (BNP) correlate with increased risk of cardiovascular events and HF development. We hypothesize that coronary sinus serum from a high BNP hypertensive population reflects an active pathological process and can be used for biomarker exploration. Our aim was to discover differentially expressed disease-associated proteins that identify patients with ventricular dysfunction and HF.; Coronary sinus serum from 11 asymptomatic, hypertensive patients underwent quantitative differential protein expression analysis by 2-dimensional difference gel electrophoresis. Proteins were identified using mass spectrometry and then studied by enzyme-linked immunosorbent assay in sera from 40 asymptomatic, hypertensive patients and 105 patients across the spectrum of ventricular dysfunction (32 asymptomatic left ventricular diastolic dysfunction, 26 diastolic HF, and 47 systolic HF patients). Leucine-rich α2-glycoprotein (LRG) was consistently overexpressed in high BNP serum. LRG levels correlate significantly with BNP in hypertensive, asymptomatic left ventricular diastolic dysfunction, diastolic HF, and systolic HF patient groups (P≤0.05). LRG levels were able to identify HF independent of BNP. LRG correlates with coronary sinus serum levels of tumor necrosis factor-α (P=0.009) and interleukin-6 (P=0.021). LRG is expressed in myocardial tissue and correlates with transforming growth factor-βR1 (P<0.001) and α-smooth muscle actin (P=0.025) expression.; LRG was identified as a serum biomarker that accurately identifies patients with HF. Multivariable modeling confirmed that LRG is a stronger identifier of HF than BNP and this is independent of age, sex, creatinine, ischemia, β-blocker therapy, and BNP.
Item Type:
Article
Language:
en
MeSH:
Actins; Aged; Asymptomatic Diseases; Biological Markers; Chi-Square Distribution; Coronary Sinus; Echocardiography, Doppler; Electrophoresis, Gel, Two-Dimensional; Enzyme-Linked Immunosorbent Assay; Female; Glycoproteins; Heart Failure; Humans; Hypertension; Immunohistochemistry; Interleukin-6; Ireland; Logistic Models; Male; Mass Spectrometry; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Protein-Serine-Threonine Kinases; Proteomics; Receptors, Transforming Growth Factor beta; Risk Assessment; Risk Factors; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left
ISSN:
1941-3297

Full metadata record

DC FieldValue Language
dc.contributor.authorWatson, Chris Jen
dc.contributor.authorLedwidge, Mark Ten
dc.contributor.authorPhelan, Dermoten
dc.contributor.authorCollier, Patricken
dc.contributor.authorByrne, Jennifer Cen
dc.contributor.authorDunn, Michael Jen
dc.contributor.authorMcDonald, Kenneth Men
dc.contributor.authorBaugh, John Aen
dc.date.accessioned2011-05-18T10:57:16Z-
dc.date.available2011-05-18T10:57:16Z-
dc.date.issued2011-03-01-
dc.identifier.citationProteomic analysis of coronary sinus serum reveals leucine-rich α2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure. 2011, 4 (2):188-97 Circ Heart Failen
dc.identifier.issn1941-3297-
dc.identifier.pmid21282491-
dc.identifier.doi10.1161/CIRCHEARTFAILURE.110.952200-
dc.identifier.urihttp://hdl.handle.net/10147/129749-
dc.description.abstractHeart failure (HF) prevention strategies require biomarkers that identify disease manifestation. Increases in B-type natriuretic peptide (BNP) correlate with increased risk of cardiovascular events and HF development. We hypothesize that coronary sinus serum from a high BNP hypertensive population reflects an active pathological process and can be used for biomarker exploration. Our aim was to discover differentially expressed disease-associated proteins that identify patients with ventricular dysfunction and HF.-
dc.description.abstractCoronary sinus serum from 11 asymptomatic, hypertensive patients underwent quantitative differential protein expression analysis by 2-dimensional difference gel electrophoresis. Proteins were identified using mass spectrometry and then studied by enzyme-linked immunosorbent assay in sera from 40 asymptomatic, hypertensive patients and 105 patients across the spectrum of ventricular dysfunction (32 asymptomatic left ventricular diastolic dysfunction, 26 diastolic HF, and 47 systolic HF patients). Leucine-rich α2-glycoprotein (LRG) was consistently overexpressed in high BNP serum. LRG levels correlate significantly with BNP in hypertensive, asymptomatic left ventricular diastolic dysfunction, diastolic HF, and systolic HF patient groups (P≤0.05). LRG levels were able to identify HF independent of BNP. LRG correlates with coronary sinus serum levels of tumor necrosis factor-α (P=0.009) and interleukin-6 (P=0.021). LRG is expressed in myocardial tissue and correlates with transforming growth factor-βR1 (P<0.001) and α-smooth muscle actin (P=0.025) expression.-
dc.description.abstractLRG was identified as a serum biomarker that accurately identifies patients with HF. Multivariable modeling confirmed that LRG is a stronger identifier of HF than BNP and this is independent of age, sex, creatinine, ischemia, β-blocker therapy, and BNP.-
dc.language.isoenen
dc.subject.meshActins-
dc.subject.meshAged-
dc.subject.meshAsymptomatic Diseases-
dc.subject.meshBiological Markers-
dc.subject.meshChi-Square Distribution-
dc.subject.meshCoronary Sinus-
dc.subject.meshEchocardiography, Doppler-
dc.subject.meshElectrophoresis, Gel, Two-Dimensional-
dc.subject.meshEnzyme-Linked Immunosorbent Assay-
dc.subject.meshFemale-
dc.subject.meshGlycoproteins-
dc.subject.meshHeart Failure-
dc.subject.meshHumans-
dc.subject.meshHypertension-
dc.subject.meshImmunohistochemistry-
dc.subject.meshInterleukin-6-
dc.subject.meshIreland-
dc.subject.meshLogistic Models-
dc.subject.meshMale-
dc.subject.meshMass Spectrometry-
dc.subject.meshMiddle Aged-
dc.subject.meshMyocardium-
dc.subject.meshNatriuretic Peptide, Brain-
dc.subject.meshProtein-Serine-Threonine Kinases-
dc.subject.meshProteomics-
dc.subject.meshReceptors, Transforming Growth Factor beta-
dc.subject.meshRisk Assessment-
dc.subject.meshRisk Factors-
dc.subject.meshTumor Necrosis Factor-alpha-
dc.subject.meshVentricular Dysfunction, Left-
dc.titleProteomic analysis of coronary sinus serum reveals leucine-rich α2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure.en
dc.typeArticleen
dc.contributor.departmentSchool of Medicine and Medical Science, St Vincent's University Hospital and The Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland.en
dc.identifier.journalCirculation. Heart failureen
dc.description.provinceLeinster-

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