Phytomedicine : international journal of phytotherapy and phytopharmacology · 2024
9-PAHSA ameliorates microvascular damage during cardiac ischaemia/reperfusion injury by promoting LKB1/AMPK/ULK1-mediated autophagy-dependent STING degradation.
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Liu Wenhu, Hu Jing, Wang Ya, Gan Ting, Ding Yan, Wang Xuehua, Xu Qian, Xiong Jingjie, Xiong Ni, Lu Shuai, Wang Yan, Wang Zhaohui
Аннотация
BACKGROUND: Considering that cardiac microvascular injury may play a more critical role than cardiomyocyte injury in the pathology of early ischaemia/reperfusion (I/R) injury, therapeutic strategies targeting the microvasculature are highly desirable. Palmitic acid-9-hydroxystearic acid (9-PAHSA) is a new class of bioactive anti-inflammatory lipids widely distributed in vegetables, fruits and medicinal plants, especially broccoli and apple. However, the pharmacological effects and underlying mechanisms of 9-PAHSA in protecting- against cardiac microvascular I/R injury have rarely been studied.
PURPOSE: This study aimed to explore the potential effects and molecular mechanisms of 9-PAHSA on the coronary microvasculature after cardiac I/R injury.
METHODS: Immunofluorescence staining, western blotting, and other experimental methods were used to evaluate the role and mechanism of 9-PAHSA in cardiac microvascular I/R injury in vivo and in vitro.
RESULTS: 9-PAHSA administration significantly attenuated myocardial I/R-induced microvascular damage, as indicated by an impaired microvascular structure, reduced regional blood perfusion and decreased endothelial barrier function. In addition, 9-PAHSA administration protected the structure and function of coronary artery endothelial cells (CMECs) to resist I/R damage, an effect that was at least partially mediated by increased autophagy. Mechanistically, 9-PAHSA activated autophagy through the LKB1/AMPK/ULK1 pathway and promoted STING degradation via the autophagic‒lysosomal pathway.
CONCLUSIONS: To our best knowledge, this study is the first to report that 9-PAHSA attenuates cardiac microvascular I/R injury, potentially by activating LKB1/AMPK/ULK1-mediated autophagy-dependent STING degradation to suppress apoptosis. Thus, 9-PAHSA may be a promising therapeutic option for alleviating cardiac microvascular I/R injury.
PURPOSE: This study aimed to explore the potential effects and molecular mechanisms of 9-PAHSA on the coronary microvasculature after cardiac I/R injury.
METHODS: Immunofluorescence staining, western blotting, and other experimental methods were used to evaluate the role and mechanism of 9-PAHSA in cardiac microvascular I/R injury in vivo and in vitro.
RESULTS: 9-PAHSA administration significantly attenuated myocardial I/R-induced microvascular damage, as indicated by an impaired microvascular structure, reduced regional blood perfusion and decreased endothelial barrier function. In addition, 9-PAHSA administration protected the structure and function of coronary artery endothelial cells (CMECs) to resist I/R damage, an effect that was at least partially mediated by increased autophagy. Mechanistically, 9-PAHSA activated autophagy through the LKB1/AMPK/ULK1 pathway and promoted STING degradation via the autophagic‒lysosomal pathway.
CONCLUSIONS: To our best knowledge, this study is the first to report that 9-PAHSA attenuates cardiac microvascular I/R injury, potentially by activating LKB1/AMPK/ULK1-mediated autophagy-dependent STING degradation to suppress apoptosis. Thus, 9-PAHSA may be a promising therapeutic option for alleviating cardiac microvascular I/R injury.