Cocaine and amphetamine-regulated transcript improves myocardial ischemia-reperfusion injury through PI3K/AKT signalling pathway.
Yachen WangZiwei WangZeyan PengLifeng FengWencong TianShengzheng ZhangLei CaoJing LiLiang YangYang XuYang GaoJie LiuJie YanXiaodong MaWangchun SunLihong GuoXuan LiYanna ShenZhi QiPublished in: Clinical and experimental pharmacology & physiology (2024)
Myocardial ischemia-reperfusion injury (MIRI) is a common clinic scenario that occurs in the context of reperfusion therapy for acute myocardial infarction. It has been shown that cocaine and amphetamine-regulated transcript (CART) can ameliorate cerebral ischemia-reperfusion (I/R) injury, but the effect of CART on MIRI has not been studied yet. Here, we revealed that CART protected the heart during I/R process by inhibiting apoptosis and excessive autophagy, indicating that CART would be a potential drug candidate for the treatment of MIRI. Further analysis showed that CART upregulated the activation of phospho-AKT, leading to downregulation of lactate dehydrogenase (LDH) release, apoptosis, oxidative stress and excessive autophagy after I/R, which was inhibited by PI3K inhibitor, LY294002. Collectively, CART attenuated MIRI through inhibition of cardiomyocytes apoptosis and excessive autophagy, and the protective effect was dependent on PI3K/AKT signalling pathway.
Keyphrases
- signaling pathway
- pi k akt
- cell cycle arrest
- oxidative stress
- ischemia reperfusion injury
- cell death
- acute myocardial infarction
- endoplasmic reticulum stress
- induced apoptosis
- cell proliferation
- left ventricular
- dna damage
- weight gain
- heart failure
- transcription factor
- rna seq
- primary care
- risk assessment
- single cell
- blood brain barrier
- climate change
- electronic health record
- smoking cessation
- drug induced
- endothelial cells