文献类型：期刊文献

英文题名：Mechanistic investigation of quercetin (an active component of RAS-RH) in modulating radiation-induced coronary microvascular dysfunction via the TCs-ECs crosstalk pathway

作者：Hugang, Jiang[1];Ai, Liu[1];Zeao, Guo[1];Ren, Chunzhen[1];Lin, Wenyan[2];Kai, Liu[3];Zhao, Xinke[1];Li, Yingdong[1]

第一作者：Hugang, Jiang

通信作者：Li, YD[1]

机构：[1]Gansu Univ Chinese Med, Sch Integrated Tradit Chinese & Western Med, Lanzhou 730000, Peoples R China;[2]Gansu Prov Peoples Hosp, Daytime Diag & Treatment Ctr, Lanzhou 730000, Peoples R China;[3]Gansu Med Coll, Sch Basic Med, Pingliang 744000, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Sch Integrated Tradit Chinese & Western Med, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2026

卷号：163

外文期刊名：MICROVASCULAR RESEARCH

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001617871300001)】；

基金：This work was supported by a grant from the Nature Science Foundations of China Grant (NO. 82374279, NO. 82360926) and Natural Science Foundation of Gansu Province (No. 23JRRA1217) . The funders had no role in study design, data collection and analysis, the decision to publish, or preparation of the manuscript.

语种：英文

外文关键词：Radix of Angelica sinensis and Hedysari ultrafiltrate (RAS-RH); Quercetin; Cardiac telocytes (TCs); Endothelial cells (ECs); Crosstalk mechanism; Coronary microvascular dysfunction (CMVD)

摘要：Background: Coronary Microvascular Dysfunction (CMVD), a prevalent comorbidity of various cardiovascular diseases, may contribute to myocardial cell ischemic necrosis. The loss of microvessels-driven by endothelial cells (ECs) apoptosis-is the core pathological hallmarks of CMVD. Our previous studies have established that RAS-RH (Angelica sinensis and Astragalus membranaceus ultrafiltrate) promotes angiogenesis and improves cardiac perfusion. However, its underlying molecular mechanisms remain incompletely understood. Purpose: This study aimed to elucidate the key mechanism by which quercetin, the primary active component of RAS-RH, modulates radiation-induced ECs apoptosis. Methods: Through the integration of network pharmacology and transcriptomics, we identified potential active components of RAS-RH and their key targets involved in regulating the telocytes-endothelial cell (TCs-ECs) crosstalk pathway underlying CMVD. These predictions were further validated using in vitro cellular models via flow cytometry, western blot, wound-healing assays, in situ hybridization, immunofluorescence staining, and EdU proliferation assays. Results: Consistent with our predictions, experimental results demonstrated that quercetin (the primary active component of RAS-RH) significantly upregulated the expression of HIF-1 alpha and miRNA-126 in TCs (P < 0.01) and enhanced miRNA-126 paracrine secretion. Through this paracrine mechanism, quercetin downregulated the expression of Cypd, ANT, F1F0-ATPase, and VDAC in ECs (P < 0.01), inhibited the reduction of mitochondrial membrane potential (Delta Psi m) and ECs apoptosis induced by excessive mPTP opening. Collectively, these effects enhanced ECs proliferation, migration, and tube formation capacity, ultimately promoting angiogenesis. Conclusion: These results collectively demonstrate that quercetin, the primary active component of RAS-RH, suppresses excessive mPTP activation and apoptosis while stimulating ECs migration and tube formation. This occurs via upregulating HIF-1 alpha and miRNA-126 expression in TCs and enhancing miRNA-126 paracrine to ECs, positioning the TCs-ECs crosstalk mechanism as a promising novel therapeutic target for intervening in coronary microcirculation dysfunction.