Document Detail


Circulating matrix metalloproteinases in adolescents with hypertrophic cardiomyopathy and ventricular arrhythmia.
MedLine Citation:
PMID:  22628530     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy (HCM) and a risk factor for ventricular arrhythmia. Fibrosis can be reflected in circulating matrix remodeling protein concentrations. We explored differences in circulating markers of extracellular matrix turnover between young HCM patients with versus without history of serious arrhythmia.
METHODS AND RESULTS: Using multiplexed and single ELISA, matrix metalloproteinases (MMPs) 1, 2, 3, and 9; tissue inhibitor of metalloproteinases (TIMPs) 1, 2, and 4; and collagen I carboxyterminal peptide (CICP) were measured in plasma from 45 young HCM patients (80% male patients; median age, 17 years [interquartile range, 15-20]). Participants were grouped into serious ventricular arrhythmia history (VA) versus no ventricular arrhythmia history (NoVA). Differences in MMPs between groups were examined nonparametrically. Relationships between MMPs and ventricular arrhythmia were assessed with linear regression, adjusted for interventricular septal thickness, family history of sudden death, abnormal exercise blood pressure, and implantable cardioverter-defibrillator (ICD). In post hoc sensitivity analysis, age was substituted for ICD. The 14 VA patients were older than 31 NoVA patients (median, 19 versus 17 years; P=0.03). All 14 VA and 12 NoVA patients had an ICD. MMP3 concentration was significantly higher in the VA group (VA median, 12.9 μg/mL [interquartile range, 5.7-16.7 μg/mL] versus NoVA, 5.8 μg/mL [interquartile range, 3.7-10.0 μg/mL]; P=0.01). On multivariable analysis, VA was independently associated with increasing MMP3 (standardized β, 0.37; P=0.01). Post hoc adjustment for age attenuated this association.
CONCLUSIONS: Circulating MMP3 may be a marker of ventricular arrhythmia in adolescent patients with HCM. Because of our role as pediatric providers, we cannot exclude age-related confounding.
Authors:
Justin P Zachariah; Steven D Colan; Peter Lang; John K Triedman; Mark E Alexander; Edward P Walsh; Charles I Berul; Frank Cecchin
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2012-05-24
Journal Detail:
Title:  Circulation. Heart failure     Volume:  5     ISSN:  1941-3297     ISO Abbreviation:  Circ Heart Fail     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-19     Completed Date:  2012-09-25     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101479941     Medline TA:  Circ Heart Fail     Country:  United States    
Other Details:
Languages:  eng     Pagination:  462-6     Citation Subset:  IM    
Affiliation:
Department of Cardiology, Children's Hospital Boston and Department of Pediatrics, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, USA. justin.zachariah@childrens.harvard.edu
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Age Factors
Biological Markers / blood
Boston
Cardiomyopathy, Hypertrophic / blood,  complications,  enzymology*,  pathology
Cross-Sectional Studies
Enzyme-Linked Immunosorbent Assay
Female
Fibrosis
Humans
Linear Models
Male
Matrix Metalloproteinase 1 / blood
Matrix Metalloproteinase 2 / blood
Matrix Metalloproteinase 3 / blood*
Matrix Metalloproteinase 9 / blood
Multivariate Analysis
Myocardium / enzymology*,  pathology
Risk Assessment
Risk Factors
Tachycardia, Ventricular / blood,  enzymology*,  etiology,  pathology
Tissue Inhibitor of Metalloproteinases / blood
Ventricular Fibrillation / blood,  enzymology*,  etiology,  pathology
Young Adult
Grant Support
ID/Acronym/Agency:
T32 HL007572/HL/NHLBI NIH HHS; T32 HL007572/HL/NHLBI NIH HHS; UL1 RR 025758/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Tissue Inhibitor of Metalloproteinases; EC 3.4.24.17/MMP3 protein, human; EC 3.4.24.17/Matrix Metalloproteinase 3; EC 3.4.24.24/MMP2 protein, human; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9; EC 3.4.24.7/MMP1 protein, human; EC 3.4.24.7/Matrix Metalloproteinase 1
Comments/Corrections

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