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Spatial phenotyping of the endocardial endothelium as a function of intracardiac hemodynamic shear stress.

Abstract：

:Despite substantial evidence for the central role of hemodynamic shear stress in the functional integrity of vascular endothelial cells, hemodynamic and molecular regulation of the endocardial endothelium lining the heart chambers remains understudied. We propose that regional differences in intracardiac hemodynamics influence differential endocardial gene expression leading to phenotypic heterogeneity of this cell layer. Measurement of intracardiac hemodynamics was performed using 4-dimensional flow MRI in healthy humans (n=8) and pigs (n=5). Local wall shear stress (WSS) and oscillatory shear indices (OSI) were calculated in three distinct regions of the LV - base, mid-ventricle (midV), and apex. In both the humans and pigs, WSS values were significantly lower in the apex and midV relative to the base. Additionally, both the apex and midV had greater oscillatory shear indices (OSI) than the base. To investigate regional phenotype, endocardial endothelial cells (EEC) were isolated from an additional 8 pigs and RNA sequencing was performed. A false discovery rate of 0.10 identified 1051 differentially expressed genes between the base and apex, and 321 between base and midV. Pathway analyses revealed apical upregulation of genes associated with translation initiation. Furthermore, tissue factor pathway inhibitor (TFPI; mean 50-fold) and prostacyclin synthase (PTGIS; 5-fold), genes prominently associated with antithrombotic protection, were consistently upregulated in LV apex. These spatio-temporal WSS values in defined regions of the left ventricle link local hemodynamics to regional heterogeneity in endocardial gene expression.

journal_name

J Biomech

journal_title

Journal of biomechanics

authors

McCormick ME,Manduchi E,Witschey WRT,Gorman RC,Gorman JH 3rd,Jiang YZ,Stoeckert CJ Jr,Barker AJ,Yoon S,Markl M,Davies PF

doi

10.1016/j.jbiomech.2016.11.018

subject

Has Abstract

pub_date

2017-01-04 00:00:00

pages

11-19

eissn

0021-9290

issn

1873-2380

pii

S0021-9290(16)31186-1

journal_volume

50

pub_type

杂志文章

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