VEGFR Endocytosis Regulates the Angiogenesis in a Mouse Model of Hindlimb Ischemia

Overview

Journal J Thorac Dis

Publisher AME Publishing Company

Specialty Pulmonary Medicine

Date 2019 Jul 10

PMID 31285877

Citations 2

Authors

Yingnan Bai

Rongle Liu

Zhixing Li

Yaqi Zhang

Xiaoyan Wang

Jian Wu

Zhuoquan Li

Sanli Qian

Bingyu Li

Zhenzhong Zhang

Abdel Hamid Fathy

Donato Cappetta

Jingmin Zhou

Yunzeng Zou

Juying Qian

Junbo Ge

Affiliations

Soon will be listed here.

Abstract

Background: The regulation of angiogenesis in the treatment of cardiovascular diseases has been widely studied and the vascular endothelial growth factor (VEGF) families and VEGF receptor (VEGFR) have been proven to be one of the key regulators. The VEGFR endocytosis has been recently proved to be involved in the regulation of angiogenesis. Our previous study showed that the upregulation of VEGFR endocytosis enhanced angiogenesis . In this research, we utilized mice with induced hindlimb ischemia, as a model to investigate the role of VEGFR endocytosis in the regulation of angiogenesis . Our goal was to observe the effect of revascularization with different degrees of VEGFR endocytosis after injecting atypical protein kinase C inhibitor (αPKCi) and dynasore, which could respectively promote and inhibit the VEGFR endocytosis.

Methods: We induced the hindlimb ischemia in adult male mice by ligating the hindlimb artery. By directly injecting the ischemic muscles with endothelial progenitor cells (EPCs) alone or EPCs + αPKCi/EPCs + dynasore or control medium (sham group), we divided the mice into four groups and detected lower limb blood flow using a laser Doppler blood perfusion imager. We also measured the immunohistochemistry (IHC) of markers for angiogenesis, such as CD31 and alpha smooth muscle actin (α-SMA) in the ischemic hindlimb tissues.

Results: We demonstrated VEGFR endocytosis played an important role in the angiogenesis of the ischemic hindlimb model . By using atypical PKC inhibitor that increase the VEGFR endocytosis, the angiogenesis in the mice model was promoted. Treatment with EPCs + αPKCi showed greater effects on blood perfusion recovery and increased the α-SMA-positive vessels.

Conclusions: The regulation of VEGFR endocytosis represents a valuable method of improving angiogenesis and thus revascularization in ischemic disease model.

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