TY - JOUR
T1 - High resolution systematic digital histological quantification of cardiac fibrosis and adipose tissue in phospholamban p.Arg14del mutation associated cardiomyopathy
AU - Gho, Johannes M. I. H.
AU - van Es, René
AU - Stathonikos, Nikolas
AU - Harakalova, Magdalena
AU - te Rijdt, Wouter P.
AU - Suurmeijer, Albert J. H.
AU - van der Heijden, Jeroen F.
AU - de Jonge, Nicolaas
AU - Chamuleau, Steven A. J.
AU - de Weger, Roel A.
AU - Asselbergs, Folkert W.
AU - Vink, Aryan
PY - 2014/4/14
Y1 - 2014/4/14
N2 - Myocardial fibrosis can lead to heart failure and act as a substrate for cardiac arrhythmias. In dilated cardiomyopathy diffuse interstitial reactive fibrosis can be observed, whereas arrhythmogenic cardiomyopathy is characterized by fibrofatty replacement in predominantly the right ventricle. The p.Arg14del mutation in the phospholamban (PLN) gene has been associated with dilated cardiomyopathy and recently also with arrhythmogenic cardiomyopathy. Aim of the present study is to determine the exact pattern of fibrosis and fatty replacement in PLN p.Arg14del mutation positive patients, with a novel method for high resolution systematic digital histological quantification of fibrosis and fatty tissue in cardiac tissue. Transversal mid-ventricular slices (n = 8) from whole hearts were collected from patients with the PLN p.Arg14del mutation (age 48±16 years; 4 (50%) male). An in-house developed open source MATLAB script was used for digital analysis of Masson's trichrome stained slides (http://sourceforge.net/projects/fibroquant/). Slides were divided into trabecular, inner and outer compact myocardium. Per region the percentage of connective tissue, cardiomyocytes and fatty tissue was quantified. In PLN p.Arg14del mutation associated cardiomyopathy, myocardial fibrosis is predominantly present in the left posterolateral wall and to a lesser extent in the right ventricular wall, whereas fatty changes are more pronounced in the right ventricular wall. No difference in distribution pattern of fibrosis and adipocytes was observed between patients with a clinical predominantly dilated and arrhythmogenic cardiomyopathy phenotype. In the future, this novel method for quantifying fibrosis and fatty tissue can be used to assess cardiac fibrosis and fatty tissue in animal models and a broad range of human cardiomyopathies. © 2014 Gho et al.
AB - Myocardial fibrosis can lead to heart failure and act as a substrate for cardiac arrhythmias. In dilated cardiomyopathy diffuse interstitial reactive fibrosis can be observed, whereas arrhythmogenic cardiomyopathy is characterized by fibrofatty replacement in predominantly the right ventricle. The p.Arg14del mutation in the phospholamban (PLN) gene has been associated with dilated cardiomyopathy and recently also with arrhythmogenic cardiomyopathy. Aim of the present study is to determine the exact pattern of fibrosis and fatty replacement in PLN p.Arg14del mutation positive patients, with a novel method for high resolution systematic digital histological quantification of fibrosis and fatty tissue in cardiac tissue. Transversal mid-ventricular slices (n = 8) from whole hearts were collected from patients with the PLN p.Arg14del mutation (age 48±16 years; 4 (50%) male). An in-house developed open source MATLAB script was used for digital analysis of Masson's trichrome stained slides (http://sourceforge.net/projects/fibroquant/). Slides were divided into trabecular, inner and outer compact myocardium. Per region the percentage of connective tissue, cardiomyocytes and fatty tissue was quantified. In PLN p.Arg14del mutation associated cardiomyopathy, myocardial fibrosis is predominantly present in the left posterolateral wall and to a lesser extent in the right ventricular wall, whereas fatty changes are more pronounced in the right ventricular wall. No difference in distribution pattern of fibrosis and adipocytes was observed between patients with a clinical predominantly dilated and arrhythmogenic cardiomyopathy phenotype. In the future, this novel method for quantifying fibrosis and fatty tissue can be used to assess cardiac fibrosis and fatty tissue in animal models and a broad range of human cardiomyopathies. © 2014 Gho et al.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84899622297&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/24732829
U2 - https://doi.org/10.1371/journal.pone.0094820
DO - https://doi.org/10.1371/journal.pone.0094820
M3 - Article
C2 - 24732829
SN - 1932-6203
VL - 9
SP - 8
EP - 8
JO - PLOS ONE
JF - PLOS ONE
IS - 4
M1 - e94820
ER -