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

Kuusisto J, Kärjä V, Sipola P, Kholová I, Peuhkurinen K, Jääskeläinen P, Naukkarinen A, Ylä-Herttuala S, Punnonen K, Laakso M - Heart (2012)

Bottom Line: Endomyocardial biopsy samples taken from the patients with HCM were compared with matched myocardial autopsy specimens.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.

View Article: PubMed Central - PubMed

Affiliation: Kuopio University Hospital, Department of Medicine/Center for Medicine and Clinical Research, Puijonlaaksontie 2, Finland. johanna.kuusisto@kuh.fi

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.

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Related in: MedlinePlus

Endomyocardial fibrosis in hypertrophic cardiomyopathy. Increased fibrosis is shown by Picrosirius Red staining (in red, asterisk). Cardiomyocytes are pale yellow stained. Original magnification ×400.
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fig3: Endomyocardial fibrosis in hypertrophic cardiomyopathy. Increased fibrosis is shown by Picrosirius Red staining (in red, asterisk). Cardiomyocytes are pale yellow stained. Original magnification ×400.

Mentions: Picrosirius collagen staining was positive in 12 of 15 HCM samples. Extensive fibrosis was found in two cases (figure 3), moderate fibrosis in four cases and mild fibrosis in six cases. In 20 control cadavers, mild fibrosis in Picrosirius staining was found in two cases.


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

Kuusisto J, Kärjä V, Sipola P, Kholová I, Peuhkurinen K, Jääskeläinen P, Naukkarinen A, Ylä-Herttuala S, Punnonen K, Laakso M - Heart (2012)

Endomyocardial fibrosis in hypertrophic cardiomyopathy. Increased fibrosis is shown by Picrosirius Red staining (in red, asterisk). Cardiomyocytes are pale yellow stained. Original magnification ×400.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3368494&req=5

fig3: Endomyocardial fibrosis in hypertrophic cardiomyopathy. Increased fibrosis is shown by Picrosirius Red staining (in red, asterisk). Cardiomyocytes are pale yellow stained. Original magnification ×400.
Mentions: Picrosirius collagen staining was positive in 12 of 15 HCM samples. Extensive fibrosis was found in two cases (figure 3), moderate fibrosis in four cases and mild fibrosis in six cases. In 20 control cadavers, mild fibrosis in Picrosirius staining was found in two cases.

Bottom Line: Endomyocardial biopsy samples taken from the patients with HCM were compared with matched myocardial autopsy specimens.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.

View Article: PubMed Central - PubMed

Affiliation: Kuopio University Hospital, Department of Medicine/Center for Medicine and Clinical Research, Puijonlaaksontie 2, Finland. johanna.kuusisto@kuh.fi

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.

Show MeSH
Related in: MedlinePlus