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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

Nuclear NF- κB activation is detected in cardiomyocytes (arrows) in hypertrophic cardiomyopathy. ×400.
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fig4: Nuclear NF- κB activation is detected in cardiomyocytes (arrows) in hypertrophic cardiomyopathy. ×400.

Mentions: NF-κB nuclear positivity was detected in eight of 15 patient endomyocardial biopsy samples. NF-κB nuclear activity was found in cardiomyocytes in four cases (three cases showed NF-κB positivity in 20–50% of nuclei, one case in 5% of nuclei) (figure 4). In three other cases, nuclear positivity of NF-κB was found in inflammatory cells. Endothelial NF-κB nuclear positivity was found in one case. In control cadaver myocardial specimens, no nuclear NF-κB positivity was detected.


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)

Nuclear NF- κB activation is detected in cardiomyocytes (arrows) in hypertrophic cardiomyopathy. ×400.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Nuclear NF- κB activation is detected in cardiomyocytes (arrows) in hypertrophic cardiomyopathy. ×400.
Mentions: NF-κB nuclear positivity was detected in eight of 15 patient endomyocardial biopsy samples. NF-κB nuclear activity was found in cardiomyocytes in four cases (three cases showed NF-κB positivity in 20–50% of nuclei, one case in 5% of nuclei) (figure 4). In three other cases, nuclear positivity of NF-κB was found in inflammatory cells. Endothelial NF-κB nuclear positivity was found in one case. In control cadaver myocardial specimens, no nuclear NF-κB positivity was detected.

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