Knockdown of IGFBP7 Alleviates High Glucose-Triggered Vascular Endothelial Injury and Is Associated With the Upregulation of AURKA in HUVECs

Liu Zd, B A Liu, Liwei Zhang, Feng Hai

Background: Progressive vascular endothelial cell (EC) injury is a key initiating event in diabetic macrovascular complications, which dramatically increases morbidity and mortality among diabetic patients by facilitating atherosclerotic lesion formation and subsequent cardio-cerebrovascular disorders. Chronic hyperglycaemia impairs endothelial proliferation, migration and angiogenic capacity; however, the key molecules regulating high glucose (HG)-mediated endothelial deterioration remain incompletely characterized. This study aimed to uncover the molecular cascade underlying HG-triggered human endothelial damage.Methods: Human umbilical vein endothelial cells (HUVECs) were randomly divided into multiple groups and incubated in medium supplemented with either physiological isotonic glucose or HG to construct an in vitro endothelial injury model induced by hyperglycaemia. Synthetic small interfering RNAs (siRNAs) were transiently transfected into HUVECs via liposomal delivery to achieve specific knockdown of insulin-like growth factor-binding protein 7 (IGFBP7) and aurora kinase A (AURKA) separately or simultaneously, with scrambled siRNA serving as the negative transfection control. After completion of drug and gene intervention, multiple sets of functional indicators (viability, migration, tube formation) and apoptotic-related molecular signatures (B-cell lymphoma 2 (Bcl-2), BCL2-associated X, apoptosis regulator (Bax), and Cleaved Caspase-3) were systematically measured to comprehensively evaluate the severity of endothelial injury.Results: HG exposure significantly impaired the fundamental biological behaviours of HUVECs, while simultaneously elevating IGFBP7 expression, depressing AURKA transcription, and tipping the equilibrium of apoptosis-related proteins: Bcl-2, Bax and Cleaved Caspase-3 (p < 0.05). Silencing IGFBP7 remarkably rescued HG-induced endothelial dysfunction, yet AURKA knockdown partly reversed these protective phenotypes (p < 0.05).Conclusion: IGFBP7 knockdown alleviates HG-induced endothelial injury, and this effect may be associated with upregulation of AURKA. These findings provide preliminary experimental evidence supporting further investigation of potential therapeutic targets for diabetic vascular complications.