Dataset Information

Genetic relevance and determinants of mitral leaflet size in hypertrophic cardiomyopathy.

ABSTRACT:

Background

Whether mitral leaflet elongation is a primary phenotype of hypertrophic cardiomyopathy (HCM) is controversial. We investigated the genetic relevance and determinants of mitral leaflet size by performing extensive gene analyses in patients with HCM.

Methods

Anterior mitral leaflet (AML) lengths were measured in HCM patients (n?=?211) and age- and sex-matched controls (n?=?30) using echocardiography with hemodynamic and chamber geometric assessments. We analyzed 82 nuclear DNA (8 sarcomeric genes, 74 other HCM-associated genes) and mitochondrial DNA. Cardiac magnetic resonance imaging (CMR) was performed in the 132 HCM patients.

Results

Average indexed AML was significantly longer for HCM than for controls (17.2?±?2.3 vs. 13.3?±?1.6?mm/m², P?2, P?=?0.025). Indexed AML was independently correlated with left atrial wall stress. The thin filament mutation group showed larger average AML (31.9?±?3.8 vs. 29.6?±?3.8?mm, P?=?0.045), but this was not significant with the indexed value. No difference in AML size among subgroups was observed based on the presence of sarcomere protein or mitochondria-related gene variants (P?>?0.05).

Conclusion

AML elongation was a unique finding of HCM. However, the leaflet size was more related to chamber geometry and hypertrophy pattern rather than genetic factors within overt HCM.

SUBMITTER: Chung H

PROVIDER: S-EPMC6819388 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Publications

Genetic relevance and determinants of mitral leaflet size in hypertrophic cardiomyopathy.

Chung Hyemoon H Kim Yoonjung Y Park Chul-Hwan CH Kim Jong-Youn JY Min Pil-Ki PK Yoon Young Won YW Kim Tae Hoon TH Lee Byoung Kwon BK Hong Bum-Kee BK Rim Se-Joong SJ Kwon Hyuck Moon HM Lee Kyung-A KA Choi Eui-Young EY

Cardiovascular ultrasound 20191028 1

<h4>Background</h4>Whether mitral leaflet elongation is a primary phenotype of hypertrophic cardiomyopathy (HCM) is controversial. We investigated the genetic relevance and determinants of mitral leaflet size by performing extensive gene analyses in patients with HCM.<h4>Methods</h4>Anterior mitral leaflet (AML) lengths were measured in HCM patients (n = 211) and age- and sex-matched controls (n = 30) using echocardiography with hemodynamic and chamber geometric assessments. We analyzed 82 nucle ...[more]

PMID: 31660989

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Project description:Rationale: Ischemic mitral regurgitation (IMR) is frequently observed following myocardial infarction (MI) and is associated with higher mortality and poor clinical prognosis if left untreated. Accumulating evidence suggests that mitral valve (MV) leaflets actively remodel post-MI, yet the cellular mechanisms underlying these responses and how this affects tissue function remain largely unknown. Objective: We sought to elucidate MV remodeling post-MI at the tissue, cellular, and transcriptomic levels. Methods and Results: The mechanical behavior of ovine MV leaflets pre-MI and 8 weeks post-MI reveal a significant decrease in radial direction extensibility, which essentially eliminated the mechanical anisotropy typically observed in healthy MVs. Quantitative histology and ultrastructural assessment by transmission electron microscopy revealed altered leaflet composition and architecture at 8 weeks post-MI. Assessment of the MV interstitial cell (MVIC) nuclear aspect ratio, a metric of cellular deformation, revealed that MVICs were on average rounder following MI. RNA sequencing (RNA-seq) indicated that YAP-induced genes were elevated at 4 weeks post-MI and genes related to extracellular matrix organization were some of the most downregulated in sheep with IMR compared to sheep without IMR at 4 weeks post-MI. Additionally, RNA-seq revealed the possible recruitment of immune cells in this remodeling process due to the drastic elevation of CXCL9 and CLEC10A. Conclusions: This multiscale assessment revealed significant mechanical and microstructural changes due to MI. RNA-seq provided a baseline for global gene expression changes in response to MI with and without IMR and suggests YAP-induced mechanotransduction, altered expression of ECM-related genes, and recruitment of immune cells as mechanisms contributing to altered MV biomechanics post-MI. Conclusions: This multiscale assessment revealed significant mechanical and microstructural changes due to MI. RNA-seq provided a baseline for global gene expression changes in response to MI with and without IMR and suggests YAP-induced mechanotransduction, altered expression of ECM-related genes, and recruitment of immune cells as mechanisms contributing to altered MV biomechanics post-MI.

Dataset Information

Genetic relevance and determinants of mitral leaflet size in hypertrophic cardiomyopathy.

Background

Methods

Results

Conclusion

Publications

Genetic relevance and determinants of mitral leaflet size in hypertrophic cardiomyopathy.

Similar Datasets

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