ORIGINAL RESEARCH article
Front. Cardiovasc. Med.
Sec. Cardiovascular Pharmacology and Drug Discovery
Volume 12 - 2025 | doi: 10.3389/fcvm.2025.1546325
This article is part of the Research TopicCommunity Series in New Mechanisms and Drugs for the Treatment of Cardiovascular Disease with Diabetes: Vol. IIView all articles
Brown adipocyte-derived exosomes in type 2 diabetes mellitus impair endothelial function via regulating intracellular calcium cycle
Provisionally accepted
- 1Ningxia Hui Autonomous Region People's Hospital, Yinchuan, China
- 2Ningxia Medical University, Yinchuan, Ningxia, China
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Background: Atherosclerosis is a leading cause of macrovascular complications in type 2 diabetes mellitus (T2DM). Lipid metabolism disorders in T2DM alter exosomal cargos, affecting vascular endothelial cells and impairing vascular endothelium-dependent relaxation.Objective: This study investigates the link between T2DM and atherosclerosis, focusing on adipose tissue-derived exosomes (AT-Exosomes) as key pathogenic factors in T2DM. Methods: AT-exosomes derived from diabetic (C57BLKS-Lepr db/db ) and non-diabetic (C57BLKS-Lepr db/+ ) mice were co-cultured with vascular aorta to evaluate pathogenicity. RNA screening in mouse aortic endothelial cells (MAECs) identified differential genes impacted by T2DM brown adipose tissue (BAT)-derived versus healthy BAT-derived exosomes. Result: BAT-derived exosomes significantly disrupted endothelium function compared to white adipose tissue (WAT)-derived exosomes. Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) gene expression in MAECs was significantly reduced in diabetic mice. Functional studies revealed that ITPR3 positively regulates the Ca 2+ /CAMKII/eNOS signaling pathway to inhibit nitric oxide (NO) release, impairing endothelial relaxation. Conclusion: BAT-derived exosomes in T2DM reduce ITPR3 expression in endothelial cells, lowering intracellular Ca 2+ and NO production, thereby contributing to vascular endotheliumdependent relaxation dysfunction. Targeting this pathway may offer therapeutic insights for T2DMassociated vascular complications.
Keywords: type 2 diabetes mellitus, endothelial dysfunction, Atherosclerosis, brown adipose tissue, Exosomes (Zhao, Zhao, He, Cai, & Pang, 2021)
Received: 16 Dec 2024; Accepted: 21 Apr 2025.
Copyright: © 2025 Ruan and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wei Zhao, Ningxia Medical University, Yinchuan, 750004, Ningxia, China
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