Reduction of Connexin 43 Attenuates Angiogenic Effects of Human Smooth Muscle Progenitor Cells via Inactivation of Akt and NF-κB Pathway

Objective: Circulating progenitor cells possess vasculogenesis property and participate in repair of vascular injury. Cx (connexin) 43—a transmembrane protein constituting gap junctions—is involved pathology. However, the role Cx43 smooth muscle (SPCs) remained unclear. Approach Results: Human SPCs cultured from CD34 + peripheral blood mononuclear expressed cell markers, such as MHC (myosin heavy chain), nonmuscle MHC, calponin, CD140B, was most abundant isoform. To evaluate SPCs, short interference RNA used to knock down expression. Cellular activities were reduced by downregulation. In addition, downregulation attenuated angiogenic potential hind limb ischemia mice. Protein array ELISA supernatant showed that IL (interleukin)-6, IL-8, HGF (hepatocyte growth factor) Simultaneously, phosphorylation NF-κB (nuclear factor kappa-light-chain-enhancer activated B cells) Akt (protein kinase B) pathway reactivation using betulinic acid, SC79 could restore secretion factors cytokines. Moreover, FAK (focal adhesion kinase)-Src (proto-oncogene tyrosine-protein Src) activation increased downregulation, inactivation Akt–NF-κB be restored Src inhibitor (PP2), indicating inactivated arose FAK-Src activation. Finally, depressed cellular after PF-562271 or PP2. Conclusions: ischemic tissue mainly through paracrine effects. Gap junction plays an important regulating function effects axis.