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 ανβ3 expression decreased after LPS stimulation. Pretreatment with anti-integrin ανβ3 antibody enhanced LPS-induced hyperpermeability. Upregulation of integrin ανβ3 decreased LPS-induced hyperpermeability. F-actin remodeling was enhanced after LPS stimulation and was inhibited by up-regulation of integrin ανβ3. 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 β3. After pretreatment with Src or Rac1 inhibitor, no significant difference was found in the expression of integrin ανβ3 in LPS-induced CMECs. These finding suggested that integrin ανβ3 overexpression decreased LPS-stimulated CMECS permeability by inhibition of cytoskeletal remodeling, but the mechanism might not be mediated via Src/Rac1 signaling.
Keywords: Integrin ανβ3; Rac1; Src; hyperpermeability; lipopolysaccharide.