Advances and challenges of targeting epicardial adipose tissue (EAT) and perivascular adipose tissue (PVAT)

Abstract Clinical consensus statements have been issued for various adipose tissues (ATs), particularly regarding the diagnostic value of epicardial AT (EAT) and perivascular AT (PVAT) in cardiovascular disease. PVAT and EAT are promising targets for drug development and many drugs were also investi...

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Main Authors: Dan Liu, Wujun Chen, Zhu Guo, Qun Gao, Bin Wang, Jie Wang, Weichao Hu, Chao Wang, Shuai Wang, Xiaolin Wu, Mantao Xu, Ganqiu Lan
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Cardiovascular Diabetology
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Online Access:https://doi.org/10.1186/s12933-025-02763-z
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author Dan Liu
Wujun Chen
Zhu Guo
Qun Gao
Bin Wang
Jie Wang
Weichao Hu
Chao Wang
Shuai Wang
Xiaolin Wu
Mantao Xu
Ganqiu Lan
author_facet Dan Liu
Wujun Chen
Zhu Guo
Qun Gao
Bin Wang
Jie Wang
Weichao Hu
Chao Wang
Shuai Wang
Xiaolin Wu
Mantao Xu
Ganqiu Lan
author_sort Dan Liu
collection DOAJ
description Abstract Clinical consensus statements have been issued for various adipose tissues (ATs), particularly regarding the diagnostic value of epicardial AT (EAT) and perivascular AT (PVAT) in cardiovascular disease. PVAT and EAT are promising targets for drug development and many drugs were also investigated, including DPP4 inhibitors, GLP-1R agonists, and SGLT-2i. Notably, DPP4 was the only gene that highly expressed in EAT and PVAT. DPP4 also reduced GLP-1 and its receptor GLP-1R expression, suggesting that DDP4 is a promising target for targeting EAT and PVAT. However, these preparations have poor specificity for PVAT and EAT. AT delivery strategies or specific AT genes, such as ADIPOQ and PHB1, may solve these problems. ADIPOQ is only expressed in AT and encodes adiponectin (ADPN). PHB1 is an AT vascular biomarker. Many ADPN and PHB1 agents have also been developed in preclinical and clinical trials. However, these agents have serious off-target effects. SaRNA, an RNA activation technology, may reduce off-target effects. Several saRNA agents were also developed in preclinical and clinical trials. Direct overexpression of ADIPOQ and PHB1 through saRNA in combination with extrahepatic delivery materials may be beneficial for drug development. This review focuses on recent advances targeting EAT and PVAT agents and identifies new therapeutic targets. Graphical abstract
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spelling doaj-art-818b622cdabb4064a4328d3deff6bb892025-08-20T03:42:44ZengBMCCardiovascular Diabetology1475-28402025-08-0124112110.1186/s12933-025-02763-zAdvances and challenges of targeting epicardial adipose tissue (EAT) and perivascular adipose tissue (PVAT)Dan Liu0Wujun Chen1Zhu Guo2Qun Gao3Bin Wang4Jie Wang5Weichao Hu6Chao Wang7Shuai Wang8Xiaolin Wu9Mantao Xu10Ganqiu Lan11Guangdong Provincial People’s Hospital, Zhuhai Hospital (Jinwan Central Hospital of Zhuhai)The Affiliated Hospital of Qingdao University, Qingdao Cancer Institute, Qingdao UniversityThe Affiliated Hospital of Qingdao University, Qingdao Cancer Institute, Qingdao UniversityThe Affiliated Hospital of Qingdao University, Qingdao Cancer Institute, Qingdao UniversityThe Affiliated Hospital of Qingdao University, Qingdao Cancer Institute, Qingdao UniversityThe Affiliated Hospital of Qingdao University, Qingdao Cancer Institute, Qingdao UniversityDepartment of Endocrinology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong UniversityThe Affiliated Hospital of Qingdao University, Qingdao Cancer Institute, Qingdao UniversityDepartment of Radiotherapy, School of Medical Imaging, Affiliated Hospital of Shandong Second Medical University, Shandong Second Medical Medical UniversityThe Affiliated Hospital of Qingdao University, Qingdao Cancer Institute, Qingdao UniversityCollege of Information Technology, Shanghai Jian Qiao University Co LtdGuangdong Provincial People’s Hospital, Zhuhai Hospital (Jinwan Central Hospital of Zhuhai)Abstract Clinical consensus statements have been issued for various adipose tissues (ATs), particularly regarding the diagnostic value of epicardial AT (EAT) and perivascular AT (PVAT) in cardiovascular disease. PVAT and EAT are promising targets for drug development and many drugs were also investigated, including DPP4 inhibitors, GLP-1R agonists, and SGLT-2i. Notably, DPP4 was the only gene that highly expressed in EAT and PVAT. DPP4 also reduced GLP-1 and its receptor GLP-1R expression, suggesting that DDP4 is a promising target for targeting EAT and PVAT. However, these preparations have poor specificity for PVAT and EAT. AT delivery strategies or specific AT genes, such as ADIPOQ and PHB1, may solve these problems. ADIPOQ is only expressed in AT and encodes adiponectin (ADPN). PHB1 is an AT vascular biomarker. Many ADPN and PHB1 agents have also been developed in preclinical and clinical trials. However, these agents have serious off-target effects. SaRNA, an RNA activation technology, may reduce off-target effects. Several saRNA agents were also developed in preclinical and clinical trials. Direct overexpression of ADIPOQ and PHB1 through saRNA in combination with extrahepatic delivery materials may be beneficial for drug development. This review focuses on recent advances targeting EAT and PVAT agents and identifies new therapeutic targets. Graphical abstracthttps://doi.org/10.1186/s12933-025-02763-zAtherosclerosisEATPVATAdipose tissue deliverysaRNAAgent development
spellingShingle Dan Liu
Wujun Chen
Zhu Guo
Qun Gao
Bin Wang
Jie Wang
Weichao Hu
Chao Wang
Shuai Wang
Xiaolin Wu
Mantao Xu
Ganqiu Lan
Advances and challenges of targeting epicardial adipose tissue (EAT) and perivascular adipose tissue (PVAT)
Cardiovascular Diabetology
Atherosclerosis
EAT
PVAT
Adipose tissue delivery
saRNA
Agent development
title Advances and challenges of targeting epicardial adipose tissue (EAT) and perivascular adipose tissue (PVAT)
title_full Advances and challenges of targeting epicardial adipose tissue (EAT) and perivascular adipose tissue (PVAT)
title_fullStr Advances and challenges of targeting epicardial adipose tissue (EAT) and perivascular adipose tissue (PVAT)
title_full_unstemmed Advances and challenges of targeting epicardial adipose tissue (EAT) and perivascular adipose tissue (PVAT)
title_short Advances and challenges of targeting epicardial adipose tissue (EAT) and perivascular adipose tissue (PVAT)
title_sort advances and challenges of targeting epicardial adipose tissue eat and perivascular adipose tissue pvat
topic Atherosclerosis
EAT
PVAT
Adipose tissue delivery
saRNA
Agent development
url https://doi.org/10.1186/s12933-025-02763-z
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