Wenhu Liu , Jing Hu , Ya Wang , Ting Gan , Yan Ding , Xuehua Wang , Qian Xu , Jingjie Xiong , Ni Xiong , Shuai Lu , Yan Wang , Zhaohui Wang
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引用次数: 0
Abstract
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.
期刊介绍：
Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.
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