Dataset Information

Kallikrein gene-modified EPCs induce angiogenesis in rats with ischemic hindlimb and correlate with integrin ?v?3 expression.

ABSTRACT:

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 ?v?3 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 ?v?3 and eNOS protein on the surface of EPCs also increased in rats with Ad/hTK-transduced EPCs. The levels of integrin ?v?3 expression were reduced by PI3K and eNOS blockade, and the inhibitor of integrin ?v?3 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 ?v?3 plays a role in the process.

SUBMITTER: Fu SS

PROVIDER: S-EPMC3760867 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Kallikrein gene-modified EPCs induce angiogenesis in rats with ischemic hindlimb and correlate with integrin αvβ3 expression.

Fu Shen Shen SS Li Fu Ji FJ Wang Yuan Yuan YY You An Bei AB Qie Yi Liang YL Meng Xiao X Li Jian Rui JR Li Bao Chuan BC Zhang Yun Y Da Li Qing Q

PloS one 20130903 9

<h4>Background</h4>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.<h4>Methods</h4>EPCs transduced with adenovirus encoding hTK-162 (i.e., Ad/hTK-transduced EPCs or Ad/GFP-tr ...[more]

PMID: 24019890

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