Low-grade inflammation and the phenotypic expression of myocardial fibrosis in hypertrophic cardiomyopathy
Open Access
- 24 March 2012
- Vol. 98 (13), 1007-1013
- https://doi.org/10.1136/heartjnl-2011-300960
Abstract
Objective To investigate the role of inflammation in the phenotypic expression of myocardial fibrosis in hypertrophic cardiomyopathy (HCM). Design Clinical study. Setting Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland. Subjects Twenty-four patients with a single HCM-causing mutation D175N in the α-tropomyosin gene and 17 control subjects. Main outcome measures Endomyocardial biopsy samples taken from the patients with HCM were compared with matched myocardial autopsy specimens. Levels of high-sensitivity C-reactive protein (hsCRP) and proinflammatory cytokines were measured in patients and controls. Myocardial late gadolinium enhancement (LGE) in cardiac MRI (CMRI) was detected. Results Endomyocardial samples in patients with HCM showed variable myocyte hypertrophy and size heterogeneity, myofibre disarray, fibrosis, inflammatory cell infiltration and nuclear factor kappa B (NF-κB) activation. Levels of hsCRP and interleukins (IL-1β, IL-1RA, IL-6, IL-10) were significantly higher in patients with HCM than in control subjects. In patients with HCM, there was a significant association between the degree of myocardial inflammatory cell infiltration, fibrosis in histopathological samples and myocardial LGE in CMRI. Levels of hsCRP were significantly associated with histopathological myocardial fibrosis. hsCRP, tumour necrosis factor α and IL-1RA levels had significant correlations with LGE in CMRI. Conclusions A variable myocardial and systemic inflammatory response was demonstrated in patients with HCM attributable to an identified sarcometric mutation. Inflammatory response was associated with myocardial fibrosis, suggesting that myocardial fibrosis in HCM is an active process modified by an inflammatory response.Keywords
This publication has 32 references indexed in Scilit:
- Insights into genotype-phenotype correlation in hypertrophic cardiomyopathy. Findings from 18 Spanish families with a single mutation in MYBPC3Heart, 2010
- Biomarkers of pathophysiology in hypertrophic cardiomyopathy: implications for clinical management and prognosisEuropean Heart Journal, 2008
- Myocardial late gadolinium enhancement is associated with raised serum amino-terminal propeptide of type III collagen concentrations in patients with hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the tropomyosin gene: magnetic resonance imaging studyHeart, 2006
- Review of Trials in Chronic Heart Failure Showing Broad-Spectrum Anti-Inflammatory ApproachesThe American Journal of Cardiology, 2005
- Analysis of Circulating Apoptosis Mediators and Proinflammatory Cytokines in Patients With Idiopathic Hypertrophic Cardiomyopathy Comparison Between Nonobstructive and Dilated-Phase Hypertrophic CardiomyopathyInternational Heart Journal, 2005
- Comparison of circulating levels of interleukin-6 and tumor necrosis factor-alpha in hypertrophic cardiomyopathy and in idiopathic dilated cardiomyopathyThe American Journal of Cardiology, 2004
- From Inflammation to Fibrosis: A Stiff Stretch of HighwayHypertension, 2004
- Inducibility of life-threatening ventricular arrhythmias is related to maximum left ventricular thickness and clinical markers of sudden cardiac death in patients with hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the α-tropomyosin geneJournal of Molecular and Cellular Cardiology, 2004
- Clinical Features of Hypertrophic Cardiomyopathy Caused by Mutation of a “Hot Spot” in the Alpha-Tropomyosin GeneJournal of the American College of Cardiology, 1997
- Increased circulating cytokines in patients with myocarditis and cardiomyopathy.Heart, 1994