Lymphangiogenesis and angiogenesis rescue murine ischemic hindlimb via transient receptor potential vanilloid 4

Hideaki Yamada; Naoaki Sakata; Tomoko Tanaka; Hideaki Tagashira; Gumpei Yoshimatsu; Ryo Kawakami; Hideichi Wada; Takahiro Iwamoto; Shohta Kodama

doi:10.1016/j.jphs.2021.04.009

Lymphangiogenesis and angiogenesis rescue murine ischemic hindlimb via transient receptor potential vanilloid 4

J Pharmacol Sci. 2021 Aug;146(4):244-248. doi: 10.1016/j.jphs.2021.04.009. Epub 2021 May 11.

Authors

Hideaki Yamada¹, Naoaki Sakata², Tomoko Tanaka², Hideaki Tagashira³, Gumpei Yoshimatsu², Ryo Kawakami², Hideichi Wada⁴, Takahiro Iwamoto³, Shohta Kodama⁵

Affiliations

¹ Department of Regenerative Medicine & Transplantation, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan, Fukuoka 814-0180, Japan; Center for Regenerative Medicine, Fukuoka University Hospital, 7-45-1 Nanakuma, Jonan, Fukuoka 814-0180, Japan; Department of Cardiovascular Surgery, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan, Fukuoka 814-0180, Japan.
² Department of Regenerative Medicine & Transplantation, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan, Fukuoka 814-0180, Japan; Research Institute for Regenerative Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan, Fukuoka 814-0180, Japan.
³ Research Institute for Regenerative Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan, Fukuoka 814-0180, Japan; Department of Pharmacology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan, Fukuoka 814-0180, Japan.
⁴ Department of Cardiovascular Surgery, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan, Fukuoka 814-0180, Japan. Electronic address: hiwada00042401@adm.fukuoka-u.ac.jp.
⁵ Department of Regenerative Medicine & Transplantation, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan, Fukuoka 814-0180, Japan; Research Institute for Regenerative Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan, Fukuoka 814-0180, Japan. Electronic address: skodama@fukuoka-u.ac.jp.

PMID: 34116738
DOI: 10.1016/j.jphs.2021.04.009

Abstract

In this study, we assessed the regulation of transient receptor potential vanilloid 4 (TRPV4) promoting lymphangio/angiogenesis to improve the ischemic hindlimb animal model, and revealed that (1) a TRPV4 agonist improved the blood flow of ischemic hindlimbs by inducing both angiogenesis and lymphangiogenesis; (2) excessive TRPV4 expression was detected on lymphatic endothelial cells (LECs) in the ischemic hindlimb; and (3) hypoxic conditions promoted Ca²⁺ influx into LECs via TRPV4. It is considered that the upregulation of both lymphatic and blood vessels by activating TRPV4 would be a promising therapeutic strategy for peripheral artery disease.

Keywords: Angiogenesis; Lymphangiogenesis; Transient receptor potential vanilloid 4 (TRPV4).

Publication types

Review

MeSH terms

Animals
Calcium / metabolism
Disease Models, Animal
Endothelial Cells / metabolism
Gene Expression Regulation, Developmental / genetics*
Hindlimb / blood supply*
Ischemia / genetics*
Ischemia / therapy*
Lymphangiogenesis / genetics*
Lymphangiogenesis / physiology*
Mice
Molecular Targeted Therapy
Neovascularization, Physiologic / genetics*
Neovascularization, Physiologic / physiology*
TRPV Cation Channels / genetics*
TRPV Cation Channels / metabolism
TRPV Cation Channels / physiology*
Up-Regulation / genetics

Substances

TRPV Cation Channels
Trpv4 protein, mouse
Calcium