TY - JOUR
T1 - Persistent Hyperactivation of Endothelial Cells in Patients with Alcoholic Hepatitis
AU - Xia, Ying
AU - Yang, Jing
AU - Sanyal, Arun J.
AU - Shah, Vijay H.
AU - Chalasani, Naga P.
AU - Yu, Qigui
AU - Zheng, Xiaoqun
AU - Li, Wei
N1 - Funding Information:
We thank the members of the TREAT consortium (Translational Research and Evolving Alcoholic Hepatits Treatment) at Indiana University (NIAAA AA021883), Mayo Clinic (NIAAA AA021788), and Virginia Commonwealth University (NIAAA AA021891); and at NIAAA (Scientific/Program Collaborator, Dr. Svetlana Raedeva), which was created with the support of the National Institute on Alcohol Abuse and Alcoholism (NIAAA U01 AA021840). This work was also funded by NIAAA grant (UH2AA026218 to Q.Y.), the grant (OPP1035237 to Q.Y.) from the Bill & Melinda Gates Foundation, the Zhejiang Provincial Natural Science Foundation of China (No. LY18H200006 to X.Z.), and Wenzhou Science and Technology Project (No. Y20180108 to X.Z.).
Funding Information:
We thank the members of the TREAT consortium (Translational Research and Evolving Alcoholic Hepatits Treatment) at Indiana University (NIAAA AA021883), Mayo Clinic (NIAAA AA021788), and Virginia Commonwealth University (NIAAA AA021891); and at NIAAA (Scientific/Program Collaborator, Dr. Svetlana Raedeva), which was created with the support of the National Institute on Alcohol Abuse and Alcoholism (NIAAA U01 AA021840). This work was also funded by NIAAA grant (UH2AA026218 to Q.Y.), the grant (OPP1035237 to Q.Y.) from the Bill & Melinda Gates Foundation, the Zhejiang Provincial Natural Science Foundation of China (No. LY18H200006 to X.Z.), and Wenzhou Science and Technology Project (No. Y20180108 to X.Z.).
Publisher Copyright:
© 2020 by the Research Society on Alcoholism
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Background: Alcoholic hepatitis (AH) is a severe inflammatory liver disease that develops in some heavy drinkers. AH patients have intense hepatic infiltration of leukocytes. Up-regulation of cell adhesion molecules (CAMs) upon endothelial cell (EC) activation plays an important role in leukocyte transendothelial migration. CAMs can shed from EC surface and accumulate in the blood, serving as soluble markers for EC activation. In this study, we examined the impact of heavy drinking on expression of soluble forms of EC activation markers (CD146, ICAM-1, VCAM-1, and VEGF-A) and the effect of alcohol abstinence on the reversal of these abnormalities in heavy drinkers with and without AH. Methods: ELISA and multiplex immunoassays were used to measure soluble EC activation markers in plasma samples from 79 AH patients, 66 heavy drinkers without overt liver disease (HDC), and 44 healthy controls (HC) at baseline, 31 AH patients and 30 HDC at 6-month follow-up, and 18 AH patients and 25 HDC at 12-month follow-up. Results: At baseline, the 4 soluble markers were significantly up-regulated in AH patients compared with HDC and HC, whereas only sVCAM-1 was elevated in HDC relative to HC. At follow-ups, plasma levels of CD146, VCAM-1, and VEGF-A remained higher in AH patients, even for those who stopped drinking. These dysregulated markers correlated with AH disease severity, clinical parameters, and several soluble inflammatory factors. Conclusions: The levels of soluble CD146, ICAM-1, VCAM-1, and VEGF-A were highly elevated in AH patients, and alcohol abstinence did not completely reverse these abnormalities.
AB - Background: Alcoholic hepatitis (AH) is a severe inflammatory liver disease that develops in some heavy drinkers. AH patients have intense hepatic infiltration of leukocytes. Up-regulation of cell adhesion molecules (CAMs) upon endothelial cell (EC) activation plays an important role in leukocyte transendothelial migration. CAMs can shed from EC surface and accumulate in the blood, serving as soluble markers for EC activation. In this study, we examined the impact of heavy drinking on expression of soluble forms of EC activation markers (CD146, ICAM-1, VCAM-1, and VEGF-A) and the effect of alcohol abstinence on the reversal of these abnormalities in heavy drinkers with and without AH. Methods: ELISA and multiplex immunoassays were used to measure soluble EC activation markers in plasma samples from 79 AH patients, 66 heavy drinkers without overt liver disease (HDC), and 44 healthy controls (HC) at baseline, 31 AH patients and 30 HDC at 6-month follow-up, and 18 AH patients and 25 HDC at 12-month follow-up. Results: At baseline, the 4 soluble markers were significantly up-regulated in AH patients compared with HDC and HC, whereas only sVCAM-1 was elevated in HDC relative to HC. At follow-ups, plasma levels of CD146, VCAM-1, and VEGF-A remained higher in AH patients, even for those who stopped drinking. These dysregulated markers correlated with AH disease severity, clinical parameters, and several soluble inflammatory factors. Conclusions: The levels of soluble CD146, ICAM-1, VCAM-1, and VEGF-A were highly elevated in AH patients, and alcohol abstinence did not completely reverse these abnormalities.
KW - Adhesion Markers
KW - Alcoholic Hepatitis
KW - Endothelial Activation
KW - Longitudinal Study
KW - Soluble Forms
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U2 - 10.1111/acer.14331
DO - 10.1111/acer.14331
M3 - Article
C2 - 32246771
AN - SCOPUS:85084067140
SN - 0145-6008
VL - 44
SP - 1075
EP - 1087
JO - Alcoholism: Clinical and Experimental Research
JF - Alcoholism: Clinical and Experimental Research
IS - 5
ER -