Kallikrein Gene-Modified EPCs Induce Angiogenesis in Rats with Ischemic Hindlimb and Correlate with Integrin αvβ3 Expression

Background Human tissue kallikrein (hTK) plays an essential role in the physiological and pathological mechanisms of blood vessels. This study aimed to determine whether angiogenesis induced by endothelial progenitor cells (EPCs) transduced with the adenovirus-mediated hTK gene could improve blood flow in rat hindlimb ischemia in vivo and to establish a promising mechanism in vitro. Methods EPCs transduced with adenovirus encoding hTK-162 (i.e., Ad/hTK-transduced EPCs or Ad/GFP-transduced EPCs) were administered to Wister rats with hindlimb ischemia through therapeutic neovascularization. Muscular capillary density (MCD), blood flow (BF), and the number of myofibers were measured at days 7, 14, and 21 after treatment. Expressions of integrin αvβ3 and endothelial nitric oxide synthase (eNOS) were detected on the surface of EPCs. Results MCD, BF, and the number of myofibers in rats with Ad/hTK-transduced EPCs remarkably increased at day 21 after treatment compared with rats with Ad/GFP-transduced EPCs or the control group (P<0.01). Expressions of integrin αvβ3 and eNOS protein on the surface of EPCs also increased in rats with Ad/hTK-transduced EPCs. The levels of integrin αvβ3 expression were reduced by PI3K and eNOS blockade, and the inhibitor of integrin αvβ3 abrogated the migration and adhesion of hTK-transduced EPCs (P<0.05). Conclusion hTK gene delivery in vivo improves the natural angiogenic response to ischemia. The ability of hTK gene-transduced EPCs can be enhanced in vitro, in which integrin αvβ3 plays a role in the process.

• Publication year

  2013

• Venue

  PLoS ONE

• Publication date

  2013-09-03

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pone.0073035PMID 24019890PMCID 3760867
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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