Liver-heart crosstalk controls IL-22 activity in cardiac protection after myocardial infarction
| Autor: | Zong Shu Xian, Ziad Mallat, Shao Fang Nie, Guo-Ping Shi, Yuan Yuan Li, Yuhua Liao, Wen Yong Dong, Zhi Peng Zeng, Yu Hu, Xiang Cheng, Jiao Jiao, Bing Jie Lv, Tingting Tang, Xin Tu, Zheng Feng Zhu, Xiang-Ping Yang, Yu Huang, Yue Han, Heng Liu, Ni Xia, Ke Wang, Min Zhang, Qing Kenneth Wang, Jing Jing Li |
|---|---|
| Přispěvatelé: | Mallat, Ziad [0000-0003-0443-7878], Apollo - University of Cambridge Repository |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cardiac function curve STAT3 Transcription Factor medicine.medical_specialty FGF21 Injections Subcutaneous Myocardial Infarction Medicine (miscellaneous) 03 medical and health sciences Mice Internal medicine medicine IL-22 Animals Regeneration liver-heart crosstalk Myocardial infarction Ventricular remodeling STAT3 Pharmacology Toxicology and Pharmaceutics (miscellaneous) biology Ventricular Remodeling business.industry Gene Expression Profiling Interleukins Heart medicine.disease Fibroblast Growth Factors Disease Models Animal 030104 developmental biology medicine.anatomical_structure Endocrinology Liver Heart failure Heart Function Tests biology.protein Ligation business Artery Research Paper |
| Zdroj: | Theranostics |
| ISSN: | 1838-7640 |
| Popis: | Interleukin (IL)-22 regulates tissue inflammation and repair. Here we report participation of the liver in IL-22-mediated cardiac repair after acute myocardial infarction (MI). Methods: We induced experimental MI in mice by ligation of the left ascending artery and evaluated the effect of IL-22 on post-MI cardiac function and ventricular remodeling. Results: Daily subcutaneous injection of 100 µg/kg mouse recombinant IL-22 for seven days attenuated adverse ventricular remodeling and improved cardiac function in mice at 28 days after left anterior descending coronary artery ligation-induced MI. Pharmacological inhibition of signal transducer and activator of transcription (STAT3) muted these IL-22 activities. While cardiomyocyte-selective depletion of STAT3 did not affect IL-22 activities in protecting post-MI cardiac injury, hepatocyte-specific depletion of STAT3 fully muted these IL-22 cardioprotective activities. Hepatocyte-derived fibroblast growth factor (FGF21) was markedly increased in a STAT3-dependent manner following IL-22 administration and accounted for the cardioprotective benefit of IL-22. Microarray analyses revealed that FGF21 controlled the expression of cardiomyocyte genes that are involved in cholesterol homeostasis, DNA repair, peroxisome, oxidative phosphorylation, glycolysis, apoptosis, and steroid responses, all of which are responsible for cardiomyocyte survival. Conclusions: Supplementation of IL-22 in the first week after acute MI effectively prevented left ventricular dysfunction and heart failure. This activity of IL-22 involved crosstalk between the liver and heart after demonstrating a role of the hepatic STAT3-FGF21 axis in IL-22-induced post-MI cardiac protection. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|