PMID- 32216615 OWN - NLM STAT- MEDLINE DCOM- 20200713 LR - 20200930 IS - 1522-1539 (Electronic) IS - 0363-6135 (Linking) VI - 318 IP - 5 DP - 2020 May 1 TI - Macrophage galectin-3 enhances intimal translocation of vascular calcification in diabetes mellitus. PG - H1068-H1079 LID - 10.1152/ajpheart.00690.2019 [doi] AB - The clinical risks and prognosis of diabetic vascular intimal calcification (VIC) and medial calcification (VMC) are different. This study aims to investigate the mechanism of VIC/VMC translocation. Anterior tibial arteries were collected from patients with diabetic foot amputation. The patients were then divided into VIC and VMC groups. There were plaques in all anterior tibial arteries, while the enrichment of galectin-3 in arterial plaques in the VIC group was significantly higher than that in the VMC group. Furthermore, a macrophage/vascular smooth muscle cell (VSMC) coculture system was constructed. VSMC-derived extracellular vesicles (EVs) was labeled with fluorescent probe. After macrophages were pretreated with recombinant galectin-3 protein, the migration of VSMC-derived EVs and VSMC-derived calcification was more pronounced. And anti-galectin-3 antibody can inhibit this process of EVs and calcification translocation. Then, lentivirus (LV)-treated bone marrow cells (BMCs) were transplanted into apolipoprotein E-deficient (ApoE(-/-)) mice, and a diabetic atherosclerosis mouse model was constructed. After 15 wk of high-fat diet, ApoE(-/-) mice transplanted with LV-shgalectin-3 BMCs exhibited medial calcification and a concentrated distribution of EVs in the media. In conclusion, upregulation of galectin-3 in macrophages promotes the migration of VSMC-derived EVs to the intima and induces diabetic vascular intimal calcification.NEW & NOTEWORTHY The clinical risk and prognosis of vascular intimal and medial calcification are different. Macrophage galectin-3 regulates the migration of vascular smooth muscle cell-derived extracellular vesicles and mediates diabetic vascular intimal/medial calcification translocation. This study may provide insights into the early intervention in diabetic vascular calcification. FAU - Sun, Zhen AU - Sun Z AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Li, Lihua AU - Li L AD - Department of Pathology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Zhang, Lili AU - Zhang L AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Yan, Jinchuan AU - Yan J AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Shao, Chen AU - Shao C AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Bao, Zhengyang AU - Bao Z AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Liu, Jia AU - Liu J AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Li, Yalan AU - Li Y AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Zhou, Mengxue AU - Zhou M AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Hou, Lina AU - Hou L AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Jing, Lele AU - Jing L AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Pang, Qiwen AU - Pang Q AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Geng, Yue AU - Geng Y AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Mao, Xiang AU - Mao X AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Gu, Wen AU - Gu W AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Wang, Zhongqun AU - Wang Z AD - Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200327 PL - United States TA - Am J Physiol Heart Circ Physiol JT - American journal of physiology. Heart and circulatory physiology JID - 100901228 RN - 0 (Apolipoproteins E) RN - 0 (Galectin 3) SB - IM MH - Aged MH - Aged, 80 and over MH - Animals MH - Apolipoproteins E/genetics MH - Cells, Cultured MH - Diabetic Angiopathies/*metabolism/pathology MH - Diabetic Cardiomyopathies/genetics/*metabolism/pathology MH - Extracellular Vesicles/metabolism MH - Female MH - Galectin 3/*metabolism MH - Humans MH - Macrophages/*metabolism MH - Male MH - Mice MH - Middle Aged MH - Myocytes, Smooth Muscle/metabolism MH - Tibial Arteries/metabolism/pathology MH - Tunica Intima/*metabolism/pathology MH - Vascular Calcification/*metabolism/pathology OTO - NOTNLM OT - extracellular vesicle OT - galectin-3 OT - macrophage OT - vascular calcification OT - vascular smooth muscle cell EDAT- 2020/03/29 06:00 MHDA- 2020/07/14 06:00 CRDT- 2020/03/29 06:00 PHST- 2020/03/29 06:00 [pubmed] PHST- 2020/07/14 06:00 [medline] PHST- 2020/03/29 06:00 [entrez] AID - 10.1152/ajpheart.00690.2019 [doi] PST - ppublish SO - Am J Physiol Heart Circ Physiol. 2020 May 1;318(5):H1068-H1079. doi: 10.1152/ajpheart.00690.2019. Epub 2020 Mar 27.