Proteomic analysis of coronary sinus serum reveals leucine-rich alpha2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure.

Hdl Handle:
http://hdl.handle.net/10147/207027
Title:
Proteomic analysis of coronary sinus serum reveals leucine-rich alpha2-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:
Circ Heart Fail. 2011 Mar;4(2):188-97. Epub 2011 Jan 31.
Journal:
Circulation. Heart failure
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207027
DOI:
10.1161/CIRCHEARTFAILURE.110.952200
PubMed ID:
21282491
Abstract:
BACKGROUND: 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. METHODS AND RESULTS: 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 alpha2-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-alpha (P=0.009) and interleukin-6 (P=0.021). LRG is expressed in myocardial tissue and correlates with transforming growth factor-betaR1 (P<0.001) and alpha-smooth muscle actin (P=0.025) expression. CONCLUSIONS: 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, beta-blocker therapy, and BNP.
Language:
eng
MeSH:
Actins/analysis; Aged; Asymptomatic Diseases; Biological Markers/blood; Chi-Square Distribution; *Coronary Sinus; Echocardiography, Doppler; Electrophoresis, Gel, Two-Dimensional; Enzyme-Linked Immunosorbent Assay; Female; Glycoproteins/*blood; Heart Failure/*blood/diagnosis/etiology; Humans; Hypertension/*blood/complications/diagnosis; Immunohistochemistry; Interleukin-6/blood; Ireland; Logistic Models; Male; Mass Spectrometry; Middle Aged; Myocardium/chemistry; Natriuretic Peptide, Brain/blood; Protein-Serine-Threonine Kinases/analysis; *Proteomics/methods; Receptors, Transforming Growth Factor beta/analysis; Risk Assessment; Risk Factors; Tumor Necrosis Factor-alpha/blood; Ventricular Dysfunction, Left/*blood/diagnosis/etiology
ISSN:
1941-3297 (Electronic); 1941-3289 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorWatson, Chris Jen_GB
dc.contributor.authorLedwidge, Mark Ten_GB
dc.contributor.authorPhelan, Dermoten_GB
dc.contributor.authorCollier, Patricken_GB
dc.contributor.authorByrne, Jennifer Cen_GB
dc.contributor.authorDunn, Michael Jen_GB
dc.contributor.authorMcDonald, Kenneth Men_GB
dc.contributor.authorBaugh, John Aen_GB
dc.date.accessioned2012-02-01T10:28:37Z-
dc.date.available2012-02-01T10:28:37Z-
dc.date.issued2012-02-01T10:28:37Z-
dc.identifier.citationCirc Heart Fail. 2011 Mar;4(2):188-97. Epub 2011 Jan 31.en_GB
dc.identifier.issn1941-3297 (Electronic)en_GB
dc.identifier.issn1941-3289 (Linking)en_GB
dc.identifier.pmid21282491en_GB
dc.identifier.doi10.1161/CIRCHEARTFAILURE.110.952200en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207027-
dc.description.abstractBACKGROUND: 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. METHODS AND RESULTS: 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 alpha2-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-alpha (P=0.009) and interleukin-6 (P=0.021). LRG is expressed in myocardial tissue and correlates with transforming growth factor-betaR1 (P<0.001) and alpha-smooth muscle actin (P=0.025) expression. CONCLUSIONS: 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, beta-blocker therapy, and BNP.en_GB
dc.language.isoengen_GB
dc.subject.meshActins/analysisen_GB
dc.subject.meshAgeden_GB
dc.subject.meshAsymptomatic Diseasesen_GB
dc.subject.meshBiological Markers/blooden_GB
dc.subject.meshChi-Square Distributionen_GB
dc.subject.mesh*Coronary Sinusen_GB
dc.subject.meshEchocardiography, Doppleren_GB
dc.subject.meshElectrophoresis, Gel, Two-Dimensionalen_GB
dc.subject.meshEnzyme-Linked Immunosorbent Assayen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshGlycoproteins/*blooden_GB
dc.subject.meshHeart Failure/*blood/diagnosis/etiologyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshHypertension/*blood/complications/diagnosisen_GB
dc.subject.meshImmunohistochemistryen_GB
dc.subject.meshInterleukin-6/blooden_GB
dc.subject.meshIrelanden_GB
dc.subject.meshLogistic Modelsen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMass Spectrometryen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshMyocardium/chemistryen_GB
dc.subject.meshNatriuretic Peptide, Brain/blooden_GB
dc.subject.meshProtein-Serine-Threonine Kinases/analysisen_GB
dc.subject.mesh*Proteomics/methodsen_GB
dc.subject.meshReceptors, Transforming Growth Factor beta/analysisen_GB
dc.subject.meshRisk Assessmenten_GB
dc.subject.meshRisk Factorsen_GB
dc.subject.meshTumor Necrosis Factor-alpha/blooden_GB
dc.subject.meshVentricular Dysfunction, Left/*blood/diagnosis/etiologyen_GB
dc.titleProteomic analysis of coronary sinus serum reveals leucine-rich alpha2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure.en_GB
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_GB
dc.identifier.journalCirculation. Heart failureen_GB
dc.description.provinceLeinster-

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