Clinical and Molecular Hepatology

"Samuel S. Lee"

Original Article

Liver fibrosis, cirrhosis, and portal hypertension

Galectin-3 inhibits cardiac contractility via a tumor necrosis factor alpha-dependent mechanism in cirrhotic rats: Ki Tae Yoon, Hongqun Liu, Jing Zhang, Sojung Han, Samuel S. Lee; Clin Mol Hepatol 2022;28(2):232-241.
Published online January 5, 2022; DOI: https://doi.org/10.3350/cmh.2021.0141

Background/Aims
Galectin-3 plays a key pathogenic role in cardiac hypertrophy and heart failure. The present study aimed to investigate the effects of galectin-3 on cardiomyopathy – related factors and cardiac contractility in a rat model of cirrhotic cardiomyopathy.
Methods
Rats were divided into two sets, one for a functional study, the other for cardiac contractile-related protein evaluation. There were four groups in each set: sham operated and sham plus N-acetyllactosamine (N-Lac, a galectin-3 inhibitor; 5 mg/kg); bile duct ligated (BDL) and BDL plus N-Lac. Four weeks after surgery, ventricular level of galectin-3, collagen I and III ratio, tumor necrosis factor alpha (TNFα), and brain natriuretic peptide (BNP) were measured either by Western blots or immunohistochemistry or enzyme-linked immunosorbent assay. Blood pressure was measured by polygraph recorder. Cardiomyocyte contractility was measured by inverted microscopy.
Results
Galectin-3 and collagen I/III ratio were significantly increased in cirrhotic hearts. TNFα and BNP were significantly increased in BDL serum and heart compared with sham controls. Galectin-3 inhibitor significantly decreased galectin-3, TNFα, and BNP in cirrhotic hearts but not in sham controls. N-Lac also significantly improved the blood pressure, and systolic and diastolic cardiomyocyte contractility in cirrhotic rats but had no effect on sham controls.
Conclusion
Increased galectin-3 in the cirrhotic heart significantly inhibited contractility via TNFα. Inhibition of galectin-3 decreased the cardiac content of TNFα and BNP and reversed the decreased blood pressure and depressed contractility in the cirrhotic heart. Galectin-3 appears to play a pathogenic role in cirrhotic cardiomyopathy.

Citations

Citations to this article as recorded by

Apoptosis in Cardiac Conditions Including Cirrhotic Cardiomyopathy
Fengxue Yu, Dae Gon Ryu, Ki Tae Yoon, Hongqun Liu, Samuel S. Lee
International Journal of Molecular Sciences.2025; 26(13): 6423. CrossRef
Cirrhotic Cardiomyopathy: Bridging Hepatic and Cardiac Pathophysiology in the Modern Era
Dragoș Lupu, Camelia Cornelia Scârneciu, Diana Țînț, Cristina Tudoran
Journal of Clinical Medicine.2025; 14(17): 5993. CrossRef
Galectin-3: A Multitasking Protein Linking Cardiovascular Diseases, Immune Disorders and Beyond
Mariarosaria Morello, Gisella Titolo, Saverio D’Elia, Silvia Caiazza, Ettore Luisi, Achille Solimene, Chiara Serpico, Andrea Morello, Francesco Natale, Paolo Golino, Plinio Cirillo, Giovanni Cimmino
Targets.2025; 3(4): 34. CrossRef
Galectin-3 as a therapeutic target in pulmonary hypertension: Molecular mechanisms, drug development directions, and emerging clinical applications
Antonín Sedlář, Pavla Bojarová, František Kolář, Vladimír Křen, Lucie Bačáková
Biomedicine & Pharmacotherapy.2025; 193: 118756. CrossRef
Cardiomyopathy in cirrhosis: From pathophysiology to clinical care
Hongqun Liu, Jwan A. Naser, Grace Lin, Samuel S. Lee
JHEP Reports.2024; 6(1): 100911. CrossRef
Cirrhotic cardiomyopathy: Pathogenesis, clinical features, diagnosis, treatment and prognosis
Francisca Almeida, Alexandra Sousa
Revista Portuguesa de Cardiologia.2024; 43(4): 203. CrossRef
Therapies for Cirrhotic Cardiomyopathy: Current Perspectives and Future Possibilities
Hongqun Liu, Daegon Ryu, Sangyoun Hwang, Samuel S. Lee
International Journal of Molecular Sciences.2024; 25(11): 5849. CrossRef
Role of Galectin in Cardiovascular Conditions including Cirrhotic Cardiomyopathy
Hongqun Liu, Sang-Youn Hwang, Samuel S. Lee
Pharmaceuticals.2023; 16(7): 978. CrossRef
Chenodeoxycholic Acid Improves Embryo Implantation and Metabolic Health through Modulating Gut Microbiota–Host Metabolites Interaction during Early Pregnancy
Meixia Chen, Ying Zhao, Haifeng Ji, Lu Li, Hui Liu, Sixin Wang, Dongyan Zhang, Jingdong Yin, Jing Wang, Xin Zhang
Antioxidants.2023; 13(1): 8. CrossRef
Temporal profile of cerebrospinal fluid galactin-3 and associated cytokine responses after severe traumatic brain injury in patients: a retrospective study
Melisa Cetin, Ping Yip, Zhou-Hao Liu
Future Healthcare Journal.2023; 10: S18. CrossRef
Temporal profile of cerebrospinal fluid galactin-3 and associated cytokine responses after severe traumatic brain injury in patients: a retrospective study
Melisa Cetin, Ping Yip, Wing Sze Leung, Zhou-Hao Liu
Clinical Medicine.2023; 23(6): 81. CrossRef
Pathogenic Mechanisms Underlying Cirrhotic Cardiomyopathy
Hongqun Liu, Henry H. Nguyen, Ki Tae Yoon, Samuel S. Lee
Frontiers in Network Physiology.2022;[Epub] CrossRef
Collagen-binding fibroblast growth factor ameliorates liver fibrosis in murine bile duct ligation injury
Qiangqiang Shi, Susu Wei, Zhi Chao Li, Jing Xu, Yaxin Li, Chuanlong Guo, Xianggen Wu, Chunying Shi, Guohu Di
Journal of Biomaterials Applications.2022; 37(5): 918. CrossRef

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Reviews

Liver fibrosis, cirrhosis, and portal hypertension

β-blockers in advanced cirrhosis: More friend than enemy: Ki Tae Yoon, Hongqun Liu, Samuel S. Lee; Clin Mol Hepatol 2021;27(3):425-436.
Published online December 3, 2020; DOI: https://doi.org/10.3350/cmh.2020.0234

Abstract
PDF

Nonselective beta-adrenergic blocker (NSBB) therapy for the prevention of initial and recurrent gastrointestinal bleeding in cirrhotic patients with gastroesophageal varices has been used for the past four decades. NSBB therapy is considered the cornerstone of treatment for varices, and has become the standard of care. However, a 2010 study from the group that pioneered β-blocker therapy suggested a detrimental effect of NSBBs in decompensated cirrhosis, especially in patients with refractory ascites. Since then, numerous additional studies have incompletely resolved whether NSBBs are deleterious, although more recent evidence weighs against a harmful effect. The possibility of a “therapeutic window” has also been raised. We aimed to review the literature to analyze the pros and cons of using NSBBs in patients with cirrhosis, not only with respect to bleeding or mortality but also to other potential benefits and risks. β-blockers are highly effective in preventing first bleeding and recurrent bleeding. Furthermore, NSBBs improve congestion/ischemia of the gut mucosa, decrease intestinal permeability, and therefore indirectly alleviate systemic inflammation. β-blockers shorten the electrocardiographic prolonged QTc interval and may also decrease the incidence of hepatocellular carcinoma. On the other hand, the possibility of deleterious effects in cirrhosis has not been completely eliminated. NSBBs may be associated with an increased risk of portal vein thrombosis, although this could be correlational artifact. Overall, we conclude that β-blockers in cirrhosis are much more of a friend than enemy.

Citations

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Hemodynamic alterations in cirrhosis and portal hypertension: Moon Young Kim, Soon Koo Baik, Samuel S. Lee; Korean J Hepatol 2010;16(4):347-352.
Published online December 31, 2010; DOI: https://doi.org/10.3350/kjhep.2010.16.4.347

Abstract
PDF

Portal hypertension (PHT) is associated with hemodynamic changes in intrahepatic, systemic, and portosystemic collateral circulation. Increased intrahepatic resistance and hyperdynamic circulatory alterations with expansion of collateral circulation play a central role in the pathogenesis of PHT. PHT is also characterized by changes in vascular structure, termed vascular remodeling, which is an adaptive response of the vessel wall that occurs in response to chronic changes in the environment such as shear stress. Angiogenesis, the formation of new blood vessels, also occurs with PHT related in particular to the expansion of portosystemic collateral circulation. The complementary processes of vasoreactivity, vascular remodeling, and angiogenesis represent important targets for the treatment of portal hypertension. Systemic and splanchnic vasodilatation can induce hyperdynamic circulation which is related with multi-organ failure such as hepatorenal syndrome and cirrhotic cadiomyopathy.

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Liver Transplantation.2017; 23(11): 1440. CrossRef
Clinical Implications of the Serum Apelin Level on Portal Hypertension and Prognosis of Liver Cirrhosis
Yoo Li Lim, Eunhee Choi, Yoon Ok Jang, Youn Zoo Cho, Yong Seok Kang, Soon Koo Baik, Sang Ok Kwon, Moon Young Kim
Gut and Liver.2016; 10(1): 109. CrossRef
Neutrophil-to-Lymphocyte Ratio Predicts Early Mortality in Patients with HBV-Related Decompensated Cirrhosis
Honggang Zhang, Qinqin Sun, Weilin Mao, Jian Fan, Bo Ye
Gastroenterology Research and Practice.2016; 2016: 1. CrossRef
AST to Platelet Ratio Index Predicts Mortality in Hospitalized Patients With Hepatitis B-Related Decompensated Cirrhosis
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Medicine.2016; 95(9): e2946. CrossRef
Dysregulated apoptosis of the venous wall in chronic venous disease and portal hypertension
Li Kun, Li Ying, Wang Lei, Zhao Jianhua, Xu Yongbo, Wang Tao, Tang Jinyuan, Chu Haibo
Phlebology: The Journal of Venous Disease.2016; 31(10): 729. CrossRef
Sodium Ferulate Reduces Portal Pressure Through Inhibition of RhoA/Rho-Kinase and Activation of Endothelial Nitric Oxide Synthase in Cirrhotic Rats
Jiqiao Liu, Liping Peng, Juan Yang, Min Wang, Shengnan Xu, Jingmei Liu, Ping Han, Jiayi He, Dean Tian, Qi Zhou
Digestive Diseases and Sciences.2015; 60(7): 2019. CrossRef
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Immunologic, hemodynamic, and adrenal incompetence in cirrhosis: impact on renal dysfunction
Louise Madeleine Risør, Flemming Bendtsen, Søren Møller
Hepatology International.2015; 9(1): 17. CrossRef
Characterization of uncommon portosystemic collateral circulations in patients with hepatic cirrhosis
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Oncology Letters.2015; 9(1): 347. CrossRef
B-cell–associated immune profiles in patients with decompensated cirrhosis
Joo Yeon Jhun, Hee Yeon Kim, Jae Kyeong Byun, Byung Ha Chung, Si Hyun Bae, Seung Kew Yoon, Dong Goo Kim, Chul Woo Yang, Mi-La Cho, Jong Young Choi
Scandinavian Journal of Gastroenterology.2015; 50(7): 884. CrossRef
Mesenteric artery responsiveness to acetylcholine and phenylephrine in cirrhotic rats challenged with endotoxin: the role of TLR4
Sattar Ostadhadi, Seyed-Mahdi Rezayat, Shahram Ejtemaei-Mehr, Seyed-Mohammad Tavangar, Vahid Nikoui, Farahnaz Jazaeri, Golnar Eftekhari, Alireza Abdollahi, Ahmad-Reza Dehpour
Canadian Journal of Physiology and Pharmacology.2015; 93(6): 475. CrossRef
Severe Portal Hypertension in Cirrhosis: Evaluation of Perfusion Parameters with Contrast-Enhanced Ultrasonography
Woo Kyoung Jeong, Tae Yeob Kim, Joo Hyun Sohn, Yongsoo Kim, Jinoo Kim, Chen-Hua Liu
PLOS ONE.2015; 10(3): e0121601. CrossRef
The influence that hepatic cirrhosis provides in exercise capacity and muscle strength: a review
Renata Lopes Krüger, Bruno Costa Teixeira, Alexandre Simões Dias, Álvaro Reischak-Oliveira
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Lin Zhai, Lan-Yan Qiu, Yuan Zu, Yan Yan, Xiao-Zhuan Ren, Jun-Feng Zhao, Yu-Jiang Liu, Ji-Bin Liu, Lin-Xue Qian
World Journal of Gastroenterology.2015; 21(15): 4509. CrossRef
Relationship between Tetrahydrobiopterin and Portal Hypertension in Patients with Chronic Liver Disease
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Journal of Korean Medical Science.2014; 29(3): 392. CrossRef
Pathophysiology of Portal Hypertension
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Clinics in Liver Disease.2014; 18(2): 281. CrossRef
Review article: the endocannabinoid system in liver disease, a potential therapeutic target
P. P. Basu, M. M. Aloysius, N. J. Shah, R. S. Brown Jr
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Stephen Fahey, Eugene Dempsey, Aideen Long
Cellular & Molecular Immunology.2014; 11(1): 25. CrossRef
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Yunqiang Cai, Zhihong Liu, Xubao Liu
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RUI XU, YU-FENG YUAN, AHMET AYAV, CHONG-QING JIANG, LAURENT BRESLER, ZHI-SU LIU, NGUYEN TRAN
Experimental and Therapeutic Medicine.2014; 7(5): 1089. CrossRef
Sodium ferulate lowers portal pressure in rats with secondary biliary cirrhosis through the RhoA/Rho-kinase signaling pathway: A preliminary study
LAI WEI, JUAN YANG, MIN WANG, SHENG-NAN XU, HUA-MIN LIANG, QI ZHOU
International Journal of Molecular Medicine.2014; 34(5): 1257. CrossRef
ANG II receptor subtype 1a gene knockdown in the subfornical organ prevents increased drinking behavior in bile duct-ligated rats
Joseph D. Walch, T. Prashant Nedungadi, J. Thomas Cunningham
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology.2014; 307(6): R597. CrossRef
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Clinical and Molecular Hepatology.2013; 19(4): 370. CrossRef
Hemodynamic effects of continuous versus bolus infusion of terlipressin for portal hypertension: A randomized comparison
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Hepatogenous Diabetes in Cirrhosis Is Related to Portal Pressure and Variceal Hemorrhage
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Digestive Diseases and Sciences.2013; 58(11): 3335. CrossRef
Influence of Nitric Oxide and cGMP on Agonist-Induced Platelet Adhesion – An In Vitro Study in Platelets Isolated from Patients with Liver Cirrhosis / Uticaj Azot-Oksida I cGMP Na Adheziju Trombocita Izazvanu Agonistima – In Vitro Studija Na Izolovanim Tr
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Intracerebroventricular losartan infusion modulates angiotensin II type 1 receptor expression in the subfornical organ and drinking behaviour in bile‐duct‐ligated rats
Joseph D. Walch, Flávia Regina Carreño, J. Thomas Cunningham
Experimental Physiology.2013; 98(4): 922. CrossRef
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Anna Gipson
Gastrointestinal Nursing.2013; 11(7): 29. CrossRef
Hepatic vein arrival time as assessed by contrast-enhanced ultrasonography is useful for the assessment of portal hypertension in compensated cirrhosis
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Hepatology.2012; 56(3): 1053. CrossRef
Comparison of Hepatic Venous Pressure Gradient and Two Models of End-stage Liver Disease for Predicting the Survival in Patients With Decompensated Liver Cirrhosis
Ki Tae Suk, Chang Hoon Kim, Seung Ha Park, Ho Taik Sung, Jong Young Choi, Kwang Hyub Han, So Hyung Hong, Dae Yong Kim, Jai Hoon Yoon, Yeon Soo Kim, Gwang Ho Baik, Jin Bong Kim, Dong Joon Kim
Journal of Clinical Gastroenterology.2012; 46(10): 880. CrossRef
Is there any vindication for low dose nonselective β-blocker medication in patients with liver cirrhosis?
Tae Wan Kim, Hong Joo Kim, Chang Uk Chon, Hyun Sun Won, Jung Ho Park, Dong Il Park, Yong Kyun Cho, Chong Il Sohn, Woo Kyu Jeon, Byung Ik Kim
Clinical and Molecular Hepatology.2012; 18(2): 203. CrossRef
PPARα activation in portal hypertension
Hongqun Liu, Samuel S. Lee, Roberto J. Groszmann, Yasuko Iwakiri, Tamar H. Taddei
Hepatology.2012; 56(5): 1993. CrossRef