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Low-grade inflammation and the phenotypic expression of myocardial fibrosis in hypertrophic cardiomyopathy.


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.

SUBMITTER: Kuusisto J 

PROVIDER: S-EPMC3368494 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Low-grade inflammation and the phenotypic expression of myocardial fibrosis in hypertrophic cardiomyopathy.

Kuusisto Johanna J   Kärjä Vesa V   Sipola Petri P   Kholová Ivana I   Peuhkurinen Keijo K   Jääskeläinen Pertti P   Naukkarinen Anita A   Ylä-Herttuala Seppo S   Punnonen Kari K   Laakso Markku M  

Heart (British Cardiac Society) 20120324 13


<h4>Objective</h4>To investigate the role of inflammation in the phenotypic expression of myocardial fibrosis in hypertrophic cardiomyopathy (HCM).<h4>Design</h4>Clinical study.<h4>Setting</h4>Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.<h4>Subjects</h4>Twenty-four patients with a single HCM-causing mutation D175N in the α-tropomyosin gene and 17 control subjects.<h4>Main outcome measures</h4>Endomyocardial biopsy samples taken from the patients with HCM were co  ...[more]

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