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Echinacoside (ECH), a phenylethanol glycoside from Tibetan herbs, was investigated for its ability to attenuate remodeling by regulating voltage-gated calcium signaling. Using hypoxia-induced HPH and monocrotaline-induced PAH models, transcriptomic data highlighted Cav1.2, Cav3.2, and PKC/MAPK enrichment, while ECH suppressed Cav1.2/Cav3.2 expression and PKC/MAPK phosphorylation, lowering mPAP and RV hypertrophy and improving vascular remodeling in both models.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/echinacoside-improves-pulmonary-vascular-remodeling-by-regulating-the-l-and-t-type-ca2-channels-research-article/456394/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/echinacoside-improves-pulmonary-vascular-remodeling-by-regulating-the-l-and-t-type-ca2-channels-research-article/456394.png","ImageObject",300,407,{"name":92,"@type":93},"Muffet","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",14,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What pathology characterizes pulmonary hypertension in this study?","Question",{"text":113,"@type":114},"Pulmonary hypertension features pulmonary vasoconstriction and irreversible pulmonary vascular remodeling, involving structural changes and cellular rearrangement in blood vessels.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Which calcium channels and signaling pathway does Echinacoside target?",{"text":118,"@type":114},"ECH regulates L- and T-type voltage-gated calcium channels, particularly Cav1.2 and Cav3.2, and modulates the PKC/MAPK signaling pathway.",{"name":120,"@type":111,"acceptedAnswer":121},"How was the effect of echinacoside evaluated in pulmonary hypertension models?",{"text":122,"@type":114},"The study used hypoxia-induced HPH and monocrotaline-induced PAH models, assessed Cav1.2/Cav3.2 expression and PKC/MAPK phosphorylation, and measured hemodynamic and remodeling outcomes including mPAP and RV hypertrophy index.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},456394,1791185026,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146,"preview_page_count":4},962090768927,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","Pulmonary Circulation  \nRESEARCH ARTICLE   \nEchinacoside Improves Pulmonary Vascular Remodeling by Regulating the L‐ and T‐Type Ca2+ Channels in the Prevention and Treatment of Pulmonary Hypertension  \nYuefu Zhao1 | Jinyu Wang1 | Yujie Qiao1 | Xiangyun Gai1  | Jiacheng Hu1 | Hongmai Wang1 | Qingqing Xia1 | Qiuqin Hu1 | Zhanqiang Li2  | Cen Li3 | Hongtao Bi3   \n1School of Pharmacy, Qinghai Minzu University, Xining, Qinghai, China | 2Qinghai University Plateau Medicine Research Center, Xining, Qinghai, China | 3Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, Qinghai, China  \nCorrespondence: Xiangyun Gai ([2015002@qhmu.edu.cn](2015002@qhmu.edu.cn))  \nReceived: 23 July 2025 | Revised: 13 December 2025 | Accepted: 29 December 2025  \nFunding: Central Government Guidance Fund for Local Science and Technology Development Program of Qinghai Province, Grant/Award Number: 2025‐ZY‐ 047; Kunlun Talents, High‐End Innovation and Entrepreneurship Leading Talents Program of Qinghai Province, Grant/Award Number: 2025  \nKeywords: echinacoside | monocrotaline | PKC/MAPK pathway | pulmonary hypertension | voltage‐gated calcium channels  \nABSTRACT  \nThe typical pathology of pulmonary hypertension (PH) is characterized by pulmonary vasoconstriction and irreversible pulmonary vascular remodeling. Vascular remodeling is the process of structural changes and cellular rearrangement of blood vessels due to injury and is a significant factor in conditions such as PH. Echinacoside (ECH) is a phenylethanol glycoside from Tibetan herbs, and our previous study found that ECH modulated calcium channels on pulmonary artery smooth muscle cells (PASMCs) and improved pulmonary vasoconstriction. To investigate the role of ECH in improving pulmonary vascular remodeling in PH, we constructed hypoxia‐induced hypoxic pulmonary hypertension (HPH) and MCT‐induced pulmonary arterial hypertension (PAH) models. Transcriptomic analysis revealed significant enrichment of Cav1.2, Cav3.2, and PKC/ MAPK signaling pathways in PAH rats. ECH effectively inhibited Cav1.2 and Cav3.2 protein and mRNA expression, as well asthe phosphorylation levels of PKC/MAPK, in HPH and PAH. In addition, ECH effectively reduced mean pulmonary artery pressure (mPAP) and right ventricular hypertrophy index (RVHI) and improved pulmonary vascular remodeling in HPH and PAH rats. In short, we found that ECH improved pulmonary vascular remodeling by modulating Cav1.2 and Cav3.2/PKC/ MAPK pathways. Furthermore, this improvement was effective in both HPH and PAH.  \n\n| Abbreviations: Akt, protein kinase B; CaM, calmodulin; Cav1 .2, abstract voltage‐dependent L‐type Ca2+ channels; Cav3 .2, abstract voltage‐dependent T‐type Ca2+ channels; DEGs, differentially expressed genes; DNB, DNA nanoballs; ECH, echinacoside; EndMT, endothelial‐mesenchymal transition; ER, endoplasmic reticulum; ERK1/2, extracellular regulated protein kinases1/2; FC, fold change; FDR, false discovery rate; GDP, guanosine diphosphate; GTP, guanosine triphosphate; HPH, hypoxic pulmonary hypertension; Il‐1β, Interleukin‐1β; Il‐6, Interleukin‐6; LA, lumen area; LTCCs, L‐type calcium channels; MCT, monocrotaline; MEK, mitogen‐activated extracellular signal‐regulated kinase; mPAP, mean pulmonary artery pressure; mTOR, mechanistic target of rapamycin; NE, norepinephrine; NF‐κB, nuclear factor κB; P38MAPK, P38 mitogen‐activated protein kinases; PAH, pulmonary arterial hypertension; PASMC, pulmonary artery smooth muscle cell; PH, pulmonary hypertension; PI3K, phosphatidylinositol 3‐kinase; PKC, protein kinase C; RELM‐β, resistin‐like molecule β; RER, rough endoplasmic reticulum; RT‐qPCR, real‐time quantitative PCR; RVHI, right ventricular hypertrophy index; STAT3, signal transducer and activator of transcription 3; TEM, transmission electron microscopy; TNF‐α, tumour necrosis factor‐alpha; TRPC1, transient receptor potential cation channel subfamily C member 1; TRPC4, transient receptor potential cation channel subfamily","cbCaioyLso5vxzDQ","https://ap.wps.com/l/cbCaioyLso5vxzDQ","pdf",6538419,17,"English","# Introduction\n## Pulmonary hypertension overview\n## PAH and HPH disease progression\n## Current therapeutic approaches","[{\"question\":\"What pathology characterizes pulmonary hypertension in this study?\",\"answer\":\"Pulmonary hypertension features pulmonary vasoconstriction and irreversible pulmonary vascular remodeling, involving structural changes and cellular rearrangement in blood vessels.\"},{\"question\":\"Which calcium channels and signaling pathway does Echinacoside target?\",\"answer\":\"ECH regulates L- and T-type voltage-gated calcium channels, particularly Cav1.2 and Cav3.2, and modulates the PKC/MAPK signaling pathway.\"},{\"question\":\"How was the effect of echinacoside evaluated in pulmonary hypertension models?\",\"answer\":\"The study used hypoxia-induced HPH and monocrotaline-induced PAH models, assessed Cav1.2/Cav3.2 expression and PKC/MAPK phosphorylation, and measured hemodynamic and remodeling outcomes including mPAP and RV hypertrophy index.\"}]","Echinacoside Improves Pulmonary Vascular Remodeling by Regulating the L- and T-Type Ca2+ Channels - Research Article | PDF",1790745922,43]