title: 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).
  
  
  METHODS
  Clinical study.
  
  
  METHODS
  Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.
  
  
  METHODS
  Twenty-four patients with a single HCM-causing mutation D175N in the α-tropomyosin gene and 17 control subjects.
  
  
  METHODS
  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.
authors.affiliation: Kuopio University Hospital, Department of Medicine/Center for Medicine and Clinical Research, Puijonlaaksontie 2, Finland. johanna.kuusisto@kuh.fi
authors.forename: Johanna
authors.initials: J
authors.lastname: Kuusisto
authors.forename: Vesa
authors.initials: V
authors.lastname: Kärjä
authors.forename: Petri
authors.initials: P
authors.lastname: Sipola
authors.forename: Ivana
authors.initials: I
authors.lastname: Kholová
authors.forename: Keijo
authors.initials: K
authors.lastname: Peuhkurinen
authors.forename: Pertti
authors.initials: P
authors.lastname: Jääskeläinen
authors.forename: Anita
authors.initials: A
authors.lastname: Naukkarinen
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
authors.forename: Kari
authors.initials: K
authors.lastname: Punnonen
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D017023:Coronary Angiography; D004247:DNA / Q000235:genetics*; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D005355:Fibrosis / Q000175:diagnosis / Q000209:etiology / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009206:Myocardium / Q000473:pathology*; D010641:Phenotype; D012720:Severity of Illness Index; D014335:Tropomyosin / Q000096:biosynthesis / Q000235:genetics*; D055815:Young Adult
chemical_list: C490775:TPM1 protein, human; D014335:Tropomyosin; D004247:DNA