Remote ischemic preconditioning reduces myocardial ischemia-reperfusion injury through unacylated ghrelin-induced activation of the JAK/STAT pathway.

Abstract

Remote ischemic preconditioning (RIPC) offers cardioprotection against myocardial ischemia-reperfusion injury. The humoral factors involved in RIPC that are released from parasympathetically innervated organs have not been identified. Previous studies showed that ghrelin, a hormone released from the stomach, is associated with cardioprotection. However, it is unknown whether or not ghrelin is involved in the mechanism of RIPC. This study aimed to determine whether ghrelin serves as one of the humoral factors in RIPC. RIPC group rats were subjected to three cycles of ischemia and reperfusion for 5 min in two limbs before left anterior descending (LAD) coronary artery ligation. Unacylated ghrelin (UAG) group rats were given 0.5 mcg/kg UAG intravenously 30 min before LAD ligation. Plasma levels of UAG in all groups were measured before and after RIPC procedures and UAG administration. Additionally, JAK2/STAT3 pathway inhibitor (AG490) was injected in RIPC and UAG groups to investigate abolishment of the cardioprotection of RIPC and UAG. Plasma levels of UAG, infarct size and phosphorylation of STAT3 were compared in all groups. Infarct size was significantly reduced in RIPC and UAG groups, compared to the other groups. Plasma levels of UAG in RIPC and UAG groups were significantly increased after RIPC and UAG administration, respectively. The cardioprotective effects of RIPC and UAG were accompanied by an increase in phosphorylation of STAT3 and abolished by AG490. This study indicated that RIPC reduces myocardial ischemia and reperfusion injury through UAG-induced activation of JAK/STAT pathway. UAG may be one of the humoral factors involved in the cardioprotective effects of RIPC.

• Authors: Yasuaki Sawashita, Naoyuki Hirata, Yusuke Yoshikawa, Hirofumi Terada, Yasuyuki Tokinaga, Michiaki Yamakage
• Journal: Basic research in cardiology (Basic Res Cardiol) Vol. 115 Issue 4 Pg. 50 (06 30 2020) ISSN: 1435-1803 [Electronic] Germany
• PMID: 32607622 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ghrelin
• STAT Transcription Factors
• Janus Kinases

Topics

• Animals
• Ghrelin (metabolism)
• Ischemic Preconditioning, Myocardial
• Janus Kinases (metabolism)
• Male
• Myocardial Reperfusion Injury (metabolism)
• Rats
• Rats, Wistar
• STAT Transcription Factors (metabolism)
• Signal Transduction (physiology)