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Proteomic analysis of coronary sinus serum reveals leucine-rich α2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure.
- Source :
-
Circulation. Heart failure [Circ Heart Fail] 2011 Mar; Vol. 4 (2), pp. 188-97. Date of Electronic Publication: 2011 Jan 31. - Publication Year :
- 2011
-
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.<br />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 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.<br />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, β-blocker therapy, and BNP.
- Subjects :
- Actins analysis
Aged
Asymptomatic Diseases
Biomarkers blood
Chi-Square Distribution
Echocardiography, Doppler
Electrophoresis, Gel, Two-Dimensional
Enzyme-Linked Immunosorbent Assay
Female
Heart Failure diagnosis
Heart Failure etiology
Humans
Hypertension complications
Hypertension diagnosis
Immunohistochemistry
Interleukin-6 blood
Ireland
Logistic Models
Male
Mass Spectrometry
Middle Aged
Myocardium chemistry
Natriuretic Peptide, Brain blood
Protein Serine-Threonine Kinases analysis
Receptor, Transforming Growth Factor-beta Type I
Receptors, Transforming Growth Factor beta analysis
Risk Assessment
Risk Factors
Tumor Necrosis Factor-alpha blood
Ventricular Dysfunction, Left diagnosis
Ventricular Dysfunction, Left etiology
Coronary Sinus
Glycoproteins blood
Heart Failure blood
Hypertension blood
Proteomics methods
Ventricular Dysfunction, Left blood
Subjects
Details
- Language :
- English
- ISSN :
- 1941-3297
- Volume :
- 4
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Circulation. Heart failure
- Publication Type :
- Academic Journal
- Accession number :
- 21282491
- Full Text :
- https://doi.org/10.1161/CIRCHEARTFAILURE.110.952200