Myoarchitectural disarray of hypertrophic cardiomyopathy begins pre-birth
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Myoarchitectural disarray of hypertrophic cardiomyopathy begins pre-birth. / Garcia-Canadilla, Patricia; Cook, Andrew C; Mohun, Timothy J; Oji, Onyedikachi; Schlossarek, Saskia; Carrier, Lucie; McKenna, William J; Moon, James C; Captur, Gabriella.
in: J ANAT, Jahrgang 235, Nr. 5, 11.2019, S. 962-976.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Myoarchitectural disarray of hypertrophic cardiomyopathy begins pre-birth
AU - Garcia-Canadilla, Patricia
AU - Cook, Andrew C
AU - Mohun, Timothy J
AU - Oji, Onyedikachi
AU - Schlossarek, Saskia
AU - Carrier, Lucie
AU - McKenna, William J
AU - Moon, James C
AU - Captur, Gabriella
N1 - © 2019 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.
PY - 2019/11
Y1 - 2019/11
N2 - Myoarchitectural disarray – the multiscalar disorganisation of myocytes, is a recognised histopathological hallmark of adult human hypertrophic cardiomyopathy (HCM). It occurs before the establishment of left ventricular hypertrophy (LVH) but its early origins and evolution around the time of birth are unknown. Our aim is to investigate whether myoarchitectural abnormalities in HCM are present in the fetal heart. We used wild-type, heterozygous and homozygous hearts (n = 56) from a Mybpc3-targeted knock-out HCM mousemodel and imaged the 3D micro-structure by high-resolution episcopic microscopy. We developed a novel structure tensor approach to extract, display and quantify myocyte orientation and its local angular uniformity by helical angle, angle of intrusion and myoarchitectural disarray index, respectively, immediately before and after birth. In wild-type, we demonstrate uniformity of orientation of cardiomyocytes with smooth transitions of helical angle transmurally both before and after birth but with traces of disarray at the septal insertion points of the right ventricle. In comparison, heterozygous mice free of LVH, and homozygous mice showed not only loss of the normal linear helical angulation transmural profiles observed in wild-type but also fewercircumferentially arranged myocytes at birth. Heterozygous and homozygous showed more disarray with a wider distribution than in wild-type before birth. In heterozygous mice, disarray was seen in the anterior, septal and inferior walls irrespective of stage, whereas in homozygous mice it extended to the whole LVcircumference including the lateral wall. In conclusion, myoarchitectural disarray is detectable in the fetal heart of an HCM mouse model before the development of LVH.
AB - Myoarchitectural disarray – the multiscalar disorganisation of myocytes, is a recognised histopathological hallmark of adult human hypertrophic cardiomyopathy (HCM). It occurs before the establishment of left ventricular hypertrophy (LVH) but its early origins and evolution around the time of birth are unknown. Our aim is to investigate whether myoarchitectural abnormalities in HCM are present in the fetal heart. We used wild-type, heterozygous and homozygous hearts (n = 56) from a Mybpc3-targeted knock-out HCM mousemodel and imaged the 3D micro-structure by high-resolution episcopic microscopy. We developed a novel structure tensor approach to extract, display and quantify myocyte orientation and its local angular uniformity by helical angle, angle of intrusion and myoarchitectural disarray index, respectively, immediately before and after birth. In wild-type, we demonstrate uniformity of orientation of cardiomyocytes with smooth transitions of helical angle transmurally both before and after birth but with traces of disarray at the septal insertion points of the right ventricle. In comparison, heterozygous mice free of LVH, and homozygous mice showed not only loss of the normal linear helical angulation transmural profiles observed in wild-type but also fewercircumferentially arranged myocytes at birth. Heterozygous and homozygous showed more disarray with a wider distribution than in wild-type before birth. In heterozygous mice, disarray was seen in the anterior, septal and inferior walls irrespective of stage, whereas in homozygous mice it extended to the whole LVcircumference including the lateral wall. In conclusion, myoarchitectural disarray is detectable in the fetal heart of an HCM mouse model before the development of LVH.
U2 - 10.1111/joa.13058
DO - 10.1111/joa.13058
M3 - SCORING: Journal article
VL - 235
SP - 962
EP - 976
JO - J ANAT
JF - J ANAT
SN - 0021-8782
IS - 5
ER -
