Endothelial Cell Remodeling and Biomarker Identification in Hypertension: Insights from Mechanical Stretch and Omics Analysis

Hypertension, a leading cause of premature death worldwide, affects approximately 1.3 billion individuals according to the WHO. It arises primarily due to excessive mechanical stretch from pulsatile blood flow on vessel walls, leading to vascular remodeling—structural and functional alterations in blood vessels. This study investigates endothelial cell (EC) responses to mechanical stretch, characterizing their role in vascular remodeling and identifying biomarkers associated with hypertension progression through omics analysis. Using human umbilical vein ECs (EA.hy926) and rat portal vein (RPV), cells were subjected to mechanical stretch for 24 hours. Immunofluorescence staining revealed significant cytoskeletal remodeling, with actin filaments aligning perpendicular to the stretch axis and an increased F-to-G actin ratio, both inhibited by Rho-associated kinase (ROCK) inhibitor Y-27632. Mechanical stretch elevated inflammatory cytokines (IL-6, IL-8, IL-1B), adhesion molecules (ICAM-1, VCAM-1, E-selectin), and reactive oxygen species (ROS). Endothelial denudation in RPV mitigated stretch-induced vascular hypertrophy, oxidative stress, and leptin expression. Proteomics analysis identified key proteins, including SRC family and CAMK2B, upregulated in hypertensive patients, with pathway analysis highlighting their role in actin cytoskeleton remodeling. Metabolomics analysis pinpointed six metabolites (e.g., HODE and linolenate) associated with hypertension risk. The findings demonstrate EC remodeling under mechanical stretch and its role in vascular pathology, providing novel insights into biomarkers and therapeutic targets for hypertension diagnosis and treatment. From Qatar University for AZ grant number IRCC-2024-497 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.