Copyright
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Strain- and sex-dependent variability in hepatic microcirculation and liver function in mice
Bing Wang, Yuan Li, Qin Ouyang, Meng-Ting Xu, Ying-Yu Wang, Sun-Jing Fu, Wei-Qi Liu, Xue-Ting Liu, Hao Ling, Xu Zhang, Rui-Juan Xiu, Ming-Ming Liu
Bing Wang, Yuan Li, Meng-Ting Xu, Ying-Yu Wang, Wei-Qi Liu, Xue-Ting Liu, Rui-Juan Xiu, Ming-Ming Liu, Institute of Microcirculation, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
Bing Wang, Yuan Li, Meng-Ting Xu, Ying-Yu Wang, Wei-Qi Liu, Xue-Ting Liu, Rui-Juan Xiu, Ming-Ming Liu, International Center of Microvascular Medicine, Chinese Academy of Medical Sciences, Beijing 100005, China
Qin Ouyang, Department of Pathology, Wangjing Hospital, China Academy of Chinese Medical Science, Beijing 100102, China
Sun-Jing Fu, Department of Cardiology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
Hao Ling, Department of Radiology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410004, Hunan Province, China
Xu Zhang, Laboratory of Electron Microscopy, Ultrastructural Pathology Center, Peking University First Hospital, Beijing 100034, China
Ming-Ming Liu, Diabetes Research Center, Chinese Academy of Medical Sciences, Beijing 100005, China
Author contributions: Liu MM conceived and designed research; Wang B, Li Y, Ouyang Q, Xu MT, Fu SJ, Wang YY performed experiments; Xu MT, Liu WQ, Fu SJ, Wang YY analyzed data; Wang B, Xu MT interpreted results of experiments; Wang B prepared figures, drafted manuscript; Liu XT, Ling H, Zhang X, Xiu RJ, Liu MM edited and revised manuscript, approved final version of manuscript.
Supported by the Beijing Municipal Natural Science Foundation, No. 7212068; and the National Natural Science Foundation of China, No. 81900747.
Institutional review board statement: This study did not involve human participants, consequently, institutional review board statement and approval, and informed consent procedures were not applicable.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Institute of Microcirculation, Chinese Academy of Medical Sciences and Peking Union Medical College (No. CAMS-IM-IACUC-2022-AE-09-17).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at
mingmingliu@imc.pumc.edu.cn.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Ming-Ming Liu, PhD, Associate Professor, Institute of Microcirculation, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 5 Dong Dan Third Alley, Dongcheng District, Beijing 100005, China.
mingmingliu@imc.pumc.edu.cn
Received: September 4, 2024
Revised: February 2, 2025
Accepted: March 26, 2025
Published online: April 21, 2025
Processing time: 226 Days and 6.5 Hours
BACKGROUND
The integrity and functionality of the hepatic microcirculation are essential for maintaining liver health, which is influenced by sex and genetic background. Understanding these variations is crucial for addressing disparities in liver disease outcomes.
AIM
To investigate the sexual dimorphism and genetic heterogeneity of liver microcirculatory function in mice.
METHODS
We assessed hepatic microhemodynamics in BALB/c, C57BL/6J, and KM mouse strains using laser Doppler flowmetry and wavelet analysis. We analyzed the serum levels of alanine transaminase, glutamic acid aminotransferase, total bile acid, total protein, alkaline phosphatase, and glucose. Histological and immunohistochemical staining were employed to quantify microvascular density and the expression levels of cluster of differentiation (CD) 31, and estrogen receptor α, and β. Statistical analyses, including the Mantel test and Pearson correlation, were conducted to determine the relationships among hepatic function, microcirculation, and marcocirculation between different sexes and across genetic backgrounds.
RESULTS
We identified sex-based disparities in hepatic microhemodynamics across all strains, with males exhibiting higher microvascular perfusion and erythrocyte concentration, but lower blood velocity. Strain-specific differences were evident, particularly in the endothelial oscillatory characteristics of the erythrocyte concentration. No sex-dependent differences in estrogen receptor expression were observed, while significant variations in CD31 expression and microvascular density were observed. The correlations highlighted relationships between hepatic microhemodynamics and liver function indicators.
CONCLUSION
Our findings indicate the influence of genetic and sex differences on hepatic microcirculation and liver function, highlighting the necessity of incorporating both genetic background and sex into hepatic physiology studies and potential liver disease management strategies.
Core Tip: This study reveals significant strain and sex-dependent variations in hepatic microcirculation among murine, highlighting the implications for liver health. Male mice exhibited higher microvascular perfusion and erythrocyte concentration, while sex-specific differences in endothelial function were indicated across strains. Cluster of differentiation 31 expression linked to microvascular density varied by sex, suggesting a role in hepatic microhemodynamics. These findings suggest the necessity of integrating genetic and sex factors into the understanding of liver physiology and pathology, potentially guiding personalized therapeutic strategies.
