Single-cell transcriptomics identifies a novel vascular barrier endothelial cell cluster under high hydrostatic pressure and hypertension

Alterations in hemodynamic forces occur in a hypertensive state, yet the effect of such mechanical stimuli, especially high hydrostatic pressure on endothelial cells is relatively understudied. Here, to simulate physiological conditions of hypertension and understand endothelial cell response, we performed single-cell RNA sequencing of endothelial cells cultured under normal (100 mmHg) and high (200 mmHg) hydrostatic pressure. We identified a distinct cluster of endothelial cells, characterized by the expression of AQP1 and GJA4, and validated the increased expression of this cell cluster under high hydrostatic pressure and in the aorta endothelium of hypertensive animals. High hydrostatic pressure also altered endothelial cell morphology and increased transcellular permeability. Through a combined analysis of hypertension-related loci identified in genome-wide association studies, we found that endothelial cell-enriched genes may mediate biological functions that contribute to the pathophysiology of hypertension. Overall, this study highlights a novel vascular barrier functional endothelial cell cluster under high hydrostatic pressure and is functionally associated with blood pressure regulation, providing insights into endothelial cell transcriptomic changes in response to high hydrostatic pressure and hypertension.