Integrin Alpha Nu Beta 3 Modulates Lipopolysaccharide-Induced Hyperpermeability In Cardiac Microvascular Endothelial Cells

Previous studies suggest an association of cardiac microvascular endothelial cells (CMECs) hyperpermeability with sepsis-related cardiac injury. Our results showed that CMECs permeability was dependent upon concentration and time of lipopolysaccharides (LPS) stimulation. Integrin alpha nu beta 3 expression decreased after LPS stimulation. Pretreatment with anti-integrin alpha nu beta 3 antibody enhanced LPS-induced hyperpermeability. Upregulation of integrin alpha nu beta 3 decreased LPS-induced hyperpermeability. F-actin remodeling was enhanced after LPS stimulation and was inhibited by up-regulation of integrin alpha nu beta 3. Inhibition of Src or Rac1 reduced CMECs permeability after LPS stimulation, but there were no differences in the phosphorylation of Src and Rac1 when over-expressing or blocking integrin beta 3. After pretreatment with Src or Rac1 inhibitor, no significant difference was found in the expression of integrin alpha nu beta 3 in LPS-induced CMECs. These finding suggested that integrin alpha nu beta 3 overexpression decreased LPS-stimulated CMECS permeability by inhibition of cytoskeletal remodeling, but the mechanism might not be mediated via Src/Rac1 signaling.