Enhanced IGF-IIRα Expression Exacerbates Lipopolysaccharide-Induced Cardiac Inflammation, Hypertrophy, and Apoptosis Through Calcineurin Activation
1
Issued Date
2024-01-01
Resource Type
ISSN
15204081
eISSN
15227278
Scopus ID
2-s2.0-85200546008
Journal Title
Environmental Toxicology
Rights Holder(s)
SCOPUS
Bibliographic Citation
Environmental Toxicology (2024)
Suggested Citation
Boonha K., Kuo W.W., Tsai B.K., Hsieh D.Y., Lin K.H., Lu S.Y., Kuo C.H., Yang L.Y., Huang C.Y. Enhanced IGF-IIRα Expression Exacerbates Lipopolysaccharide-Induced Cardiac Inflammation, Hypertrophy, and Apoptosis Through Calcineurin Activation. Environmental Toxicology (2024). doi:10.1002/tox.24385 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/100461
Title
Enhanced IGF-IIRα Expression Exacerbates Lipopolysaccharide-Induced Cardiac Inflammation, Hypertrophy, and Apoptosis Through Calcineurin Activation
Author's Affiliation
China Medical University College of Medicine
School of Medicine
Faculty of Tropical Medicine, Mahidol University
Tzu Chi University of Science and Technology
University of Taipei
Chung Shan Medical University Hospital
Asia University
China Medical University Hospital
Chung Shan Medical University
Hualien Tzu Chi Hospital
William & Mary
Soochow University
China Medical University
School of Medicine
Faculty of Tropical Medicine, Mahidol University
Tzu Chi University of Science and Technology
University of Taipei
Chung Shan Medical University Hospital
Asia University
China Medical University Hospital
Chung Shan Medical University
Hualien Tzu Chi Hospital
William & Mary
Soochow University
China Medical University
Corresponding Author(s)
Other Contributor(s)
Abstract
Cardiovascular disease is one of the leading causes of death worldwide and has a high prevalence. Insulin-like growth factor-II receptor α (IGF-IIRα) acts as a stress-inducible negative regulator. This study focused on the substantial impact of heightened expression of IGF-IIRα in cardiac myoblasts and its association with the exacerbation of cardiac dysfunction. Using lipopolysaccharide (LPS)-induced H9c2 cardiac myoblasts as a model for sepsis, we aimed to elucidate the molecular interactions between IGF-IIRα and LPS in exacerbating cardiac injury. Our findings demonstrated a synergistic induction of cardiac inflammation and hypertrophy by LPS stimulation and IGF-IIRα overexpression, leading to decreased cell survival. Excessive calcineurin activity, triggered by this combined condition, was identified as a key factor exacerbating the negative effects on cell survival. Cellular changes such as cell enlargement, disrupted actin filaments, and upregulation of hypertrophy-related and inflammation-related proteins contributed to the overall hypertrophic and inflammatory responses. Overexpression of IGF-IIRα also exacerbated apoptosis induced by LPS in H9c2 cardiac myoblasts. Inhibiting calcineurin in LPS-treated H9c2 cardiac myoblasts with IGF-IIRα overexpression effectively reversed the detrimental effects, reducing cell damage and mitigating apoptosis-related cardiac mechanisms. Our study suggests that under sepsis-like conditions in the heart with IGF-IIRα overexpression, hyperactivation of calcineurin worsens cardiac damage. Suppressing IGF-IIRα and calcineurin expression could be a potential intervention to alleviate the impact of the illness and improve cardiac function.