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

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.