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Ghrelin inhibited pressure overload–induced cardiac hypertrophy by promoting autophagy via CaMKK/AMPK signaling pathway
- Source :
- Peptides. 136:170446
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Ghrelin, a novel gut hormone, has been shown to exert protective effects on cardiac dysfunction and remodeling. However, the underlying mechanisms of its protective effects remain unclear. Here, we investigated the effects of ghrelin on cardiac hypertrophy and explored the mechanisms involved. Ghrelin (30 μg.kg-1. day-1) was systemically administered to rats with cardiac hypertrophy induced by abdominal aortic constriction (AAC) by a mini-osmotic pump the next day after surgery continuously for 4 weeks. The AAC treated rats without ghrelin infusion showed decreased ghrelin content and expression of its receptors in the hearts. Exogenous ghrelin greatly attenuated cardiac hypertrophy as shown by heart weight to tibial length (HW/TL), hemodynamics, echocardiography, histological analyses, and expression of hypertrophic markers induced by AAC. This corresponded with decreased cardiac fibrosis and inflammation in the hearts of AAC rats treated with ghrelin. Moreover, ghrelin significantly increased the myocardial expression of autophagy markers, which was further confirmed in cultured cardiomyocytes. Concurrently, cardiomyocyte apoptosis in vivo and in vitro was ameliorated by ghrelin, which was reversed by inhibition of autophagy. The enhancement of autophagy and inhibition of apoptosis by ghrelin were eliminated on pretreatment with compound C, an AMP-activated protein kinase (AMPK) inhibitor. Furthermore, inhibition of Ca2+/Calmodulin-dependent protein kinase kinase (CaMKK), an upstream kinase of AMPK, made ghrelin fail to activate AMPK and simultaneously reversed ghrelin's promotion of autophagy. In conclusion, ghrelin could exert its cardioprotective effects on cardiac hypertrophy by promoting autophagy, possibly via CaMKK/AMPK signaling pathway.
- Subjects :
- medicine.medical_specialty
Cardiotonic Agents
Physiology
Cardiac fibrosis
Apoptosis
Calcium-Calmodulin-Dependent Protein Kinase Kinase
Cardiomegaly
030209 endocrinology & metabolism
Constriction, Pathologic
Biochemistry
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Endocrinology
AMP-Activated Protein Kinase Kinases
AMP-activated protein kinase
Internal medicine
Autophagy
Pressure
medicine
Animals
Humans
Aorta, Abdominal
Receptor
Protein kinase A
Pressure overload
biology
business.industry
digestive, oral, and skin physiology
AMPK
medicine.disease
Ghrelin
Rats
Disease Models, Animal
biology.protein
business
hormones, hormone substitutes, and hormone antagonists
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- ISSN :
- 01969781
- Volume :
- 136
- Database :
- OpenAIRE
- Journal :
- Peptides
- Accession number :
- edsair.doi.dedup.....361137f6afaa25def4111f8e49ba689a