Activation of TRPV4 Increases Neovascularization of Rat Prefabricated Flaps

Jinhong Bae; Zhichao Wang; Haizhou Li; Lin Lu; Qingxiong Yu; Qingfeng Li; Zan Tao

doi:10.1055/s-0037-1607210

Journal of Reconstructive Microsurgery, Table of Contents

J Reconstr Microsurg 2018; 34(01): 035-040
DOI: 10.1055/s-0037-1607210

Original Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Activation of TRPV4 Increases Neovascularization of Rat Prefabricated Flaps

Jinhong Bae^*

¹Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China

,

Zhichao Wang^*

¹Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China

,

Haizhou Li

¹Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China

,

Lin Lu

¹Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China

,

Qingxiong Yu

¹Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China

,

Qingfeng Li

¹Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China

,

Zan Tao

¹Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China

› Author Affiliations

Abstract

Background Inadequate neovascularization is a major risk factor that can lead to subsequent necrosis of prefabricated flaps. Recent evidence indicates that transient receptor potential cation channel, subfamily V, member 4 (TRPV4) activates growth and remodeling of collateral arteries in ischemia tissues by responding to elevated fluid shear stress (FSS). Therefore, we evaluated whether TRPV4 could increase neovascularization in prefabricated flaps in a rat model.

Methods Rat prefabricated skin flaps were created by ligating the right femoral vascular pedicle and implanting it underneath abdominal flaps. Thirty-six male Sprague–Dawley rats were randomly assigned to three groups with different solutions injected subcutaneously in the implantation site around the pedicle: injected with normal saline as the control group; injected with 4α-Phorbol 12,13-didecanoate (4αPDD), a specific TRPV4 activator, as the 4αPDD group; or injected with ruthenium red (RR), a TRPV-blocker, as the RR group. Neovascularization was evaluated by laser speckle contrast imaging (FLPI), histological staining, and enzyme-linked immunosorbent assay (ELISA) within two weeks. Afterwards, the abdominal island flaps were completely elevated and sutured back. The flap viability and survival area were examined on day 7.

Results A larger area of flap survival, higher capillary densities, and higher von Willebrand factor (vWF) expression were observed in the 4αPDD group in comparison to those in the other two groups. The secretion of vascular endothelial growth factor (VEGF), but not basic fibroblast growth factor (bFGF), was significantly elevated in the 4αPDD group.

Conclusion Activation of TRPV4 using 4αPDD can significantly increase the survival of prefabricated flaps via neovascularization inducement, possibly through VEGF secretion enhancement. TRPV4 serves as a potential therapeutic neovascularization target in prefabricated flaps.

Keywords

TRPV4 - prefabricated flaps - neovascularization - vascular endothelial growth factor

Full Text

References

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