Aim: During hypertension-induced endothelial dysfunction, periodic mechanical stretching (MS) activates related inflammatory pathways and leads to endothelial damage, but the underlying mechanisms remain unknown. The present study aimed to determine the injury of HUVECs caused by overstretching and the role of HMGB1-RAGE pathway in HUVECs after injury.
Main methods and key findings: Human umbilical vein endothelial cells (HUVECs) were cultured and seeded in BioFlex™ plates (six wells). Cells were exposed to 5% (physiological state) and 20% (pathological state) mechanical stretch at 1 Hz for 12 or 24 h in a Flexcell-5000™, with unstretched cells serving as controls. It was found that excessive MS can inhibit cell viability, proliferation, and tube-forming ability resulting in disordered cell arrangement and orientation, slowing cell migration. All these changes cause endothelial damage compared to physiological MS. Endothelial cells (ECs) promote cell migration and self-repair after injury by increasing the High-mobility group box 1 (HMGB1) expression. Experiments and protein prediction networks have shown that HMGB1 can also promote the expression of downstream protein bFGF by binding to receptor for advanced glycation end products (RAGE). Interestingly, VEGF protein expression did not change significantly during this repair process, implying that bFGF replaces the role of VEGF in vascular endothelial repair.
Significance: The present study demonstrates that in the context of endothelial injury caused by excessive MS, the HMGB1/RAGE/bFGF pathway is activated and promotes endothelial repair after injury. Therefore, understanding these mechanisms will help find new therapies for diseases such as hypertension, atherosclerosis, and aneurysm formation.
Keywords: Basic fibroblast growth factor; High-mobility group box 1; Human umbilical vein endothelial cells; Hypertension; Mechanical stretching; Receptor for advanced glycation end products.
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