Exacerbation of Hepatic Damage in Endothelial Aquaporin 1 Transgenic Mice after Experimental Heatstroke

• Published in: Biomedicines Vol. 12; no. 9; p. 2057
• Main Authors: Yanagisawa, Kaoru, Miyamoto, Kazuyuki, Wakayama, Yoshihiro, Arata, Satoru, Suzuki, Keisuke, Nakamura, Motoyasu, Yamaga, Hiroki, Miyazaki, Takuro, Honda, Kazuho, Dohi, Kenji, Ohtaki, Hirokazu
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.09.2024; MDPI
• Subjects: Aquaporin 1; Aquaporins; BCG; BCG vaccines; Blood vessels; Brain; Electrolytes; Endothelial cells; Endothelium; Genetic engineering; Global warming; Heat; Heatstroke; Hepatocytes; Homeostasis; Immunoreactivity; Liver; Liver diseases; Localization; macrophage; mouse; Nitrotyrosine; Relative humidity; Thermal cycling; Transgenic mice; Japan; United States > US; Germany; heatstroke; mouse; macrophage; aquaporin 1; liver
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines12092057

Heatstroke induces fluid loss and electrolyte abnormalities owing to high ambient temperature (AT) and relative humidity (RH). Aquaporin 1 (AQP1) is a key protein for water homeostasis; however, its role in heatstroke remains unclear. This study examines endothelial AQP1 in Tie2-Cre/LNL-AQP1 double transgenic (dTG) mice with upregulated Aqp1 in endothelial cells. For experimental heatstroke, mice were exposed to 41 °C AT and >99% RH. Blood, brain, kidney, and liver samples were collected 24 h later. Blood was analyzed for electrolytes and tissue damage markers, and organs were examined using morphological and immunohistological staining for 3-nitrotyrosine (3-NT), AQP1, and Iba-1. No difference in Aqp1 expression was observed in the whole brain; however, it was detected in dTG mice after capillary deprivation. AQP1 immunostaining revealed immunoreaction in blood vessels. After heat exposure, wild-type and dTG mice showed electrolyte abnormalities compared with non-heatstroke wild-type mice. Hepatic damage markers were significantly higher in dTG mice than in wild-type mice. Hematoxylin-eosin staining and 3-NT immunoreactivity in the liver indicated hepatic damage. The number of Iba-1-positive cells adherent to hepatic vasculature was significantly higher in dTG mice than in wild-type mice. This study is the first to suggest that endothelial AQP1 contributes to hepatic damage after heatstroke.