Résumé
Tissue repair after myocardial infarction involves complex mechanical cues that influence both cell and extracellular matrix gene expression. Achieving a balance between adaptive heart muscle remodeling and fibrosis is crucial for post-infarction tissue outcome. Speckle tracking echocardiography can provide detailed regional mechanical data to explore potential links between atypical forces and subsequent fibrosis during heart tissue remodeling.
Evaluate the predictive potential of early post-infarction regional wall motion parameters assessed by speckle tracking echocardiography on global gene expression program and the occurrence of myocardial fibrosis in corresponding regions.
Using a murine myocardial infarction model, mechanical stresses were determined at day 5 post-infarction through speckle tracking analysis (VevoStrain) in 29 mice. Hearts were harvested 30days later, and echocardiographic projections and tissue sections were segmented into matched 48 circumferential ventricular regions. Speckle tracking data were related to the presence of fibrosis (picrosirius staining, n=29), and consecutive tissue sections were used to link fibrosis with specific gene expression by spatial transcriptomic analysis (Visium, 10X Genomics, n=12).
Stepwise regression (29 mice) identified 13 motion regional parameters (out of 48) at day 5 that were predictive for fibrosis in the corresponding regions at day 30 (AUC=0.82). Moreover, 60% of the transcriptome significantly correlated with at least one motion parameter. Shear, radial strain, and strain rate exhibited the strongest correlations, particularly with genes related to cytoskeleton and extracellular matrix formation, but also with those involved in immunity and metabolism.
Speckle tracking analysis of regional motion parameters demonstrates extraordinary potential in predicting fibrosis occurrence, unveiling the wide mechanobiological coupling in the heart post-infarction. Understanding the mechanical cues responsible for inappropriate, fibrotic remodeling could lead to evidence-based treatments targeting involved pathways, ultimately improving patient management after infarction.