Vascular-type heterogeneity is associated with differential gene expression profiles of endothelial cells under shear stress.

BACKGROUND: Endothelial cell (EC) heterogeneity is an emerging area of research in EC biology. Vein, artery, and microvascular ECs have been shown to have heterogeneity in gene expression and function, termed "vascular-type" heterogeneity in this report. In addition to this innate heterogeneity, we hypothesized that different vascular-type ECs would also demonstrate heterogeneity in their response to shear stress. OBJECTIVES: We interrogated whether vascular-type ECs would demonstrate variations in transcriptional expression patterns under shear stress. METHODS: Human umbilical vein ECs, human pulmonary arterial ECs, and human microvascular ECs were commercially purchased and subjected to 0, 1, 4, and 10 dynes/cm(2) of laminar shear stress. After shear stress exposure, cellular alignment was analyzed, and RNA was extracted and evaluated via bulk RNA sequencing. RESULTS: All ECs demonstrated significant changes in alignment under shear stress. Shear stress significantly affected the transcriptomes of ECs, resulting in differential expression of genes and pathways. While several genes were differentially expressed by all 3 vascular EC types (44.2%), most differentially expressed genes were limited to 1 or 2 of the vascular types. Hemostatic and thrombotic genes were found to have differential expression patterns under conditions of shear stress, and von Willebrand factor demonstrated a pattern of vascular-type heterogeneity in response to shear stress. CONCLUSION: Shear stress causes changes in cellular alignment and transcriptional patterns in ECs that are dependent upon underlying vascular type. Therefore, endothelial vascular-type heterogeneity can regulate response to shear stress, especially in hemostatic and thrombotic gene expression.