Hypercapnia Accelerates Wound Healing in Endothelial Cell Monolayers Exposed to Hypoxia

Takao Tsuji 1, Kazutetsu Aoshiba*, 1, Masayuki Itoh 1, Hiroyuki Nakamura 1, Kazuhiro Yamaguchi 2
1 Department of Respiratory Medicine, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuou, Ami, Inashiki, Ibaraki 300-0395, Japan
2 Comprehensive and Internal Medicine, Tokyo Women's Medical University Medical Center East, 2-1-10 nishi-ogu, Arakawa-ku, Tokyo 116-8567, Japan

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© Tsuji et al.; Licensee Bentham Open.

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* Address correspondence to this author at the Department of Respiratory Medicine, Tokyo Medical University Ibaraki Medical Center3-20-1, Chuou, Ami, Inashiki, Ibaraki 300-0395, Japan; Tel: 81-29-887-1161; Fax 81-29-888-3463; E-mail:



While tissue hypoxia is known to play a critical role in the process of vascular injury and repair, the effect of hypercapnia on this process remains uncertain. We investigated whether hypercapnia might influence endothelial cell wound healing under the influence of hypoxia.

Materials and Methodology:

Monolayers of human umbilical venous endothelial cells (HUVECs) were scratch-wounded and incubated under different levels of O2, CO2, and pH in the environment.


Inhibition of wound healing was observed in the HUVEC monolayers under the hypoxic condition as compared to the normoxic condition. Both hypercapnic acidosis and buffered hypercapnia, but not normocapnic acidosis improved the rate of wound healing under the influence of hypoxia. The beneficial effect of hypercapnia was associated with stimulation of cell proliferation, without effects on cell adhesion, migration or apoptosis. On the other hand, the stimulatory effect of hypercapnia on wound healing and cell proliferation was not noted under normoxic conditions.


These results suggest that hypercapnia, rather than acidosis per se, accelerated the wound healing in HUVEC monolayers cultured under hypoxic conditions. The effect of hypercapnia on wound healing was due, at least in part, to the stimulation of cell proliferation by hypercapnia.

Keywords: Endothelial cell, hypoxia, hypercapnia, acidosis, wound healing..