IGFBP7 mediates oxLDL-induced human vascular endothelial cell injury by suppressing the expression of SIRT1

Area of Science:

• Cardiovascular Biology
• Endothelial Cell Function
• Atherosclerosis Pathogenesis

Background:

• Endothelial cell injury is a key initiator of atherosclerotic lesion formation.
• Insulin-like growth factor binding protein 7 (IGFBP7) influences tumor-associated endothelial cell behavior.
• The role of IGFBP7 in atherosclerosis-related endothelial cell injury remains unclear.

Purpose of the Study:

• To investigate the involvement of IGFBP7 in endothelial cell injury during atherosclerosis.
• To elucidate the mechanisms by which IGFBP7 affects endothelial cells in an atherosclerosis context.

Main Methods:

• Human aortic endothelial cells (HAECs) were treated with oxidized low-density lipoprotein (oxLDL) to simulate atherosclerosis.
• IGFBP7 expression was modulated using small interfering RNA (siRNA) and recombinant IGFBP7 protein.
• Cellular apoptosis, inflammation, and protein expression (SIRT1) were assessed.
• Immunofluorescence was used to determine IGFBP7 and CD93 co-localization.

Main Results:

• Oxidized low-density lipoprotein (oxLDL) significantly upregulated IGFBP7 expression in HAECs.
• Knockdown of IGFBP7 or inhibition with anti-IGFBP7 antibody attenuated oxLDL-induced apoptosis and inflammation.
• Recombinant IGFBP7 promoted HAEC apoptosis and inflammation, correlating with CD93 co-localization.
• IGFBP7 mediated injury via CD93 interaction and SIRT1 downregulation in an autocrine manner, with SIRT1 overexpression rescuing the phenotype.

Conclusions:

• IGFBP7 is induced by oxLDL and contributes to oxLDL-induced endothelial cell apoptosis and inflammation.
• IGFBP7 exerts its pro-apoptotic and pro-inflammatory effects through interaction with CD93 and suppression of SIRT1.
• Targeting IGFBP7 presents a potential therapeutic avenue for preventing atherosclerosis.