Ghrelin inhibits myocardial pyroptosis in diabetic cardiomyopathy by regulating ERS and NLRP3 inflammasome crosstalk through the PI3K/AKT pathway.

Abstract

AIMS:

Endoplasmic reticulum stress(ERS) can induce inflammation mediated by NLRP3 inflammatory bodies and link inflammation with oxidative stress in myocardial tissue. Ghrelin is an endogenous growth hormone-releasing peptide that has been proven to have multiple effects, such as regulating energy metabolism and inhibiting inflammation. However, the role of ghrelin in myocardial injury in diabetic rats and the mechanism have not been reported.

RESULTS:

We found that ghrelin could improve endoplasmic reticulum stress and inflammatory pyroptosis in the myocardial tissue of diabetic rats and reduce ERS and NLRP3 inflammasome crosstalk in H9C2 cardiomyocytes. Interestingly, ghrelin could activate the PI3K/AKT signalling pathway, playing a role in inhibiting endoplasmic reticulum stress and reducing the expression of pyroptosis-related proteins. However, these protective effects could be largely eliminated by LY294002.

CONCLUSIONS:

In summary, we demonstrated that ghrelin inhibited myocardial pyroptosis in diabetic cardiomyopathy by regulating ERS and NLRP3 inflammasome crosstalk through the PI3K/AKT pathway. Our results provide new insights into the mechanism of diabetic myocardial injury induced by high glucose and high palmitic acid and ghrelin-mediated anti-inflammatory protection and provide potential therapeutic targets and strategies for diabetic cardiomyopathy.

• Authors: Fan Wang, Jingzhi Wang, Xinfang Liang, Zixuan Wu, Jiaxin Xue, Lingyu Yin, Lai Wei, Xiaohui Zhang
• Journal: Journal of drug targeting (J Drug Target) Vol. 32 Issue 2 Pg. 148-158 (Dec 2024) ISSN: 1029-2330 [Electronic] England
• PMID: 38088811 (Publication Type: Journal Article)

Chemical References

• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• gamma-aminobutyryl-2-methyltryptophyl-2-methyltryptophyl-2-methyltryptophyl-lysinamide
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Ghrelin
• Reactive Oxygen Species
• Oligopeptides

Topics

• Rats
• Animals
• Inflammasomes (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Diabetic Cardiomyopathies (drug therapy)
• Pyroptosis
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Diabetes Mellitus, Experimental (drug therapy)
• Ghrelin (pharmacology, therapeutic use)
• Reactive Oxygen Species (metabolism)
• Inflammation (drug therapy)
• Oligopeptides