Dec 6, 2019

Mitral valve leaflet response to ischemic mitral regurgitation: From gene expression to tissue remodeling

BioRxiv : the Preprint Server for Biology
Daniel P HowsmonMichael S Sacks

Abstract

Aims: Ischemic mitral regurgitation is frequently observed following myocardial infarction and is associated with higher mortality and poor clinical prognosis if left untreated. Accumulating evidence suggests that mitral valve leaflets actively remodel post-myocardial infarction, yet the cellular mechanisms underlying these responses and how this affects tissue function remain largely unknown. We sought to elucidate mitral valve remodeling post myocardial infarction at the tissue, cellular, and transcriptomic levels. Methods and Results: The mechanical behavior of ovine mitral valve leaflets pre- and 8 weeks post-myocardial infarction reveal a significant decrease in radial direction extensibility, which essentially eliminated the mechanical anisotropy typically observed in healthy mitral valves. Quantitative histology and ultrastructural assessment by transmission electron microscopy revealed altered leaflet composition and architecture at 8 weeks post-myocardial infarction. Assessment of the mitral valve interstitial cell nuclear aspect ratio, a metric of cellular deformation, revealed that they were on average rounder following myocardial infarction. RNA sequencing indicated that YAP-induced genes were elevated at 4 weeks po...Continue Reading

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Mentioned in this Paper

Interstitial Cell
Immune Effector Cell
Histology Procedure
Genes
Mitral Valve
Sequence Determinations, RNA
Extracellular Matrix
Mechanotransduction, Cellular
Myocardial Infarction
Leaflet of Mitral Valve

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