Ontology highlight
ABSTRACT: Background
Salvia miltiorrhiza is used extensively to treat cardiovascular diseases. SAA is a major bioactive component in Salvia miltiorrhiza and mediates myocardial ischemia (MI). However, the industrial production of SAA is limited due to low yields. In addition, the direct targets of SAA are unknown. Here we explore cardioprotective mechanisms and targets of SAA in the cardiovascular system.Methods
Transgelin and actin were identified as targets of SAA using a chemical biology method and were validated by Biacore analysis, microscale thermophoresis and single-molecule imaging. Studies of transgelin (-/-) knockout mice further verify the target. Cardioprotective mechanisms and targets of SAA were studied in cultured vascular smooth muscle cells and transgenic mice.Findings
In WT mice, SAA targeted transgelin and had a protective effect on myocardium but did not have the same protective effect on transgelin (-/-) mice. SAA stabilizes the transgelin-actin complex, modulates the reorganization of the actin cytoskeleton, facilitates F-actin bundling, further enhances the contractility and blood flows of coronary arteries, and improves outcomes of myocardial ischemia. Based on the target, a more active SAA derivative offering myocardial protection, SAA-30, was obtained.Interpretation
We report on the direct targets of SAA and mechanisms of myocardial ischemia treatment. We also find that transgelin may act as a novel therapeutic target of myocardial ischemia. Furthermore, a more effective derivative of SAA provides the basis for further clinical translational research.
SUBMITTER: Zhong W
PROVIDER: S-EPMC6286650 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
Zhong Weilong W Sun Bo B Gao Wenqing W Qin Yuan Y Zhang Heng H Huai Longcong L Tang Yuanhao Y Liang Yuan Y He Lingfei L Zhang Xiaoyun X Tao Honglian H Chen Shuang S Yang Wei W Yang Lan L Liu Yanrong Y Liu Huijuan H Zhou Honggang H Sun Tao T Yang Cheng C
EBioMedicine 20181023
<h4>Background</h4>Salvia miltiorrhiza is used extensively to treat cardiovascular diseases. SAA is a major bioactive component in Salvia miltiorrhiza and mediates myocardial ischemia (MI). However, the industrial production of SAA is limited due to low yields. In addition, the direct targets of SAA are unknown. Here we explore cardioprotective mechanisms and targets of SAA in the cardiovascular system.<h4>Methods</h4>Transgelin and actin were identified as targets of SAA using a chemical biolog ...[more]