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Liver-heart crosstalk controls IL-22 activity in cardiac protection after myocardial infarction
- Source :
- Theranostics
- Publication Year :
- 2018
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 18387640
- Volume :
- 8
- Issue :
- 16
- Database :
- OpenAIRE
- Journal :
- Theranostics
- Accession number :
- edsair.doi.dedup.....dfab28dbfecd744a51b0453b74e0fd36