Vascular wall microenvironment: Endothelial cells original exosomes mediated melatonin-suppressed vascular calcification and vascular ageing in a m6A methylation dependent manner.

Autor:	Shan SK; National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China., Lin X; Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, 410011, People's Republic of China., Wu F; Department of Pathology, The Second Xiangya Hospital of Central South University, Changsha, 410011, People's Republic of China., Li CC; National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China., Guo B; National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China., Li FX; National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China., Zheng MH; National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China., Wang Y; National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China., Xu QS; National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China., Lei LM; National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China., Tang KX; National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China., Wu YY; National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China., Duan JY; National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China., Cao YC; National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China., Wu YL; National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China., Tan CM; Department of Cardiothoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, People's Republic of China., Liu ZH; Department of Cardiothoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, People's Republic of China., Zhou ZA; Department of Cardiothoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, People's Republic of China., Liao XB; Department of Cardiothoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, People's Republic of China., Xu F; National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China., Yuan LQ; National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China.
Jazyk:	angličtina
Zdroj:	Bioactive materials [Bioact Mater] 2024 Aug 28; Vol. 42, pp. 52-67. Date of Electronic Publication: 2024 Aug 28 (Print Publication: 2024).
DOI:	10.1016/j.bioactmat.2024.08.021
Abstrakt:	Vascular calcification and vascular ageing are "silent" diseases but are highly prevalent in patients with end stage renal failure and type 2 diabetes, as well as in the ageing population. Melatonin (MT) has been shown to induce cardiovascular protection effects. However, the role of MT on vascular calcification and ageing has not been well-identified. In this study, the aortic transcriptional landscape revealed clues for MT related cell-to-cell communication between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in vascular calcification and vascular ageing. Furthermore, we elucidated that it was exosomes that participate in the information transportation from ECs to VSMCs. The exosomes secreted from melatonin-treated ECs (MT-ECs-Exos) inhibited calcification and senescence of VSMCs. Mechanistically, miR-302d-5p was highly enriched in MT-ECs-Exos, while depletion of miR-302d-5p blocked the ability of MT-ECs-Exos to suppress VSMC calcification and senescence. Notably, Wnt3 was a bona fide target of miR-302d-5p and modulated VSMC calcification and senescence. Furthermore, we found that maturation of endothelial derived exosomal miR-302d-5p was promoted by WTAP in an N 6 -methyladenosine (m 6 A)-dependent manner. Interestingly, MT alleviated vascular calcification and ageing in 5/6-nephrectomy (5/6 NTP) mice, a chronic kidney disease (CKD) induced vascular calcification and vascular ageing mouse model. MT-ECs-Exos was absorbed by VSMCs in vivo and effectively prevented vascular calcification and ageing in 5/6 NTP mice. ECs-derived miR-302d-5p mediated MT induced anti-calcification and anti-ageing effects in 5/6 NTP mice. Our study suggests that MT-ECs-Exos alleviate vascular calcification and ageing through the miR-302d-5p/Wnt3 signaling pathway, dependent on m 6 A methylation. (© 2024 The Authors.)
Databáze:	MEDLINE
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