Spatial and temporal variations in hemodynamic forces initiate cardiac trabeculation

JCI Insight
Juhyun LeeTzung K Hsiai

Abstract

Hemodynamic shear force has been implicated as modulating Notch signaling-mediated cardiac trabeculation. Whether the spatiotemporal variations in wall shear stress (WSS) coordinate the initiation of trabeculation to influence ventricular contractile function remains unknown. Using light-sheet fluorescent microscopy, we reconstructed the 4D moving domain and applied computational fluid dynamics to quantify 4D WSS along the trabecular ridges and in the groves. In WT zebrafish, pulsatile shear stress developed along the trabecular ridges, with prominent endocardial Notch activity at 3 days after fertilization (dpf), and oscillatory shear stress developed in the trabecular grooves, with epicardial Notch activity at 4 dpf. Genetic manipulations were performed to reduce hematopoiesis and inhibit atrial contraction to lower WSS in synchrony with attenuation of oscillatory shear index (OSI) during ventricular development. γ-Secretase inhibitor of Notch intracellular domain (NICD) abrogated endocardial and epicardial Notch activity. Rescue with NICD mRNA restored Notch activity sequentially from the endocardium to trabecular grooves, which was corroborated by observed Notch-mediated cardiomyocyte proliferations on WT zebrafish trabecul...Continue Reading

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Citations

Jan 27, 2019·Journal of Cardiovascular Development and Disease·Nicholas A BattistaLaura A Miller
Jan 15, 2021·Journal of Cell Science·Oscar M J A StassenCecilia M Sahlgren
Feb 4, 2021·Annals of Biomedical Engineering·Nabid SalehinCheng-Jen Chuong
Feb 13, 2021·Journal of Cardiovascular Development and Disease·Huseyin Enes Salman, Huseyin Cagatay Yalcin
Jun 29, 2021·Frontiers in Cardiovascular Medicine·Bohan ZhangJuhyun Lee
Jun 26, 2021·Briefings in Functional Genomics·Jeannette C HallabMirana Ramialison
Aug 30, 2019·Journal of Vascular Research·Rongsong LiTzung K Hsiai
Jan 14, 2022·Biomechanics and Modeling in Mechanobiology·Haifeng WangFathollah Varnik

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Methods Mentioned

BETA
fluorescence microscopy
transgenic
PCR
confocal microscopy

Software Mentioned

MeshMixer
Amira
Mathworks
TetGen
SimVascular
ImageJ

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