کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5032124 1471114 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Spatial phenotyping of the endocardial endothelium as a function of intracardiac hemodynamic shear stress
ترجمه فارسی عنوان
فنوتیپی فضایی اندوتلیوم اندوکرین به عنوان تابع برشی همودینامیک داخل شکمی
موضوعات مرتبط
مهندسی و علوم پایه سایر رشته های مهندسی مهندسی پزشکی
چکیده انگلیسی

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Biomechanics - Volume 50, 4 January 2017, Pages 11-19
نویسندگان
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