MSCs Contribute to the Conversion of [Ly6C.sup.high] Monocytes into [Ly6C.sup.low] Subsets under AMI

• Published in: Stem cells international 2020-01, Vol.2020
• Main Authors: Lu, Wenbin, Ma, Genshan, Sheng, Zulong, Wang, Qingjie, Chen, Lijuan, Qi, Junhua, Shi, Ronghui, Ji, Jingjing, Ji, Zhenjun, Dai, Qiming
• Format: Article
• Language: English
• Subjects: Comparative analysis; Ethylenediaminetetraacetic acid; Mice
• ISSN: 1687-9678
• DOI: 10.1155/2020/2460158

Background. [Ly6C.sup.high] monocytes are inflammatory cells that accumulate in an infarcted myocardium, and [Ly6C.sup.low] monocytes are believed to be reparative and curb myocardial remodeling. NR4A1 is a novel target for modulating the inflammatory phenotype of monocytes during atherogenesis. Objectives. We aimed to investigate whether MSCs can contribute to the heterogeneity of [Ly6C.sup.high] monocytes differentiated into [Ly6C.sup.low] monocytes and whether this regulation is related to nuclear receptor NR4A1. Methods. [Ly6C.sup.high/low] monocytes were first cocultured with MSCs. [C57BL/6.sup.CX3CR1-/-] mice and C57BL/6 wild-type mice were then used to construct AMI models, and survival functions in the two groups were further compared. [Ly6C.sup.high/low] monocytes in circulation and in MI tissue of [C57BL/6.sup.CX3CR1-/-] AMI mice with or without MSC transplantation were determined by flow cytometry at day 1 and day 3. NR4A1 expression was further determined by Western blot. Apoptosis of cardiac myocytes in the infarct border zone at day 3 and day 7 was identified by TUNEL kits. Angiogenesis in the AMI heart at day 7 and day 21 was determined through immunohistochemistry by CD31. Results. We first demonstrated that the percentage of [Ly6C.sup.low] monocytes increased greatly after 3 days of coculture with MSCs (12.8% [+ or -] 3.77% vs. 3.69% [+ or -] 0.74%, p < 0.001). The expression of NR4A1 in [Ly6C.sup.high/low] monocytes was also significantly elevated at that time (1.81 [+ or -] 0.46 vs. 0.43 [+ or -] 0.09, p < 0.001). Following AMI, the percentage of circulating [Ly6C.sup.low] monocytes in [C57BL/6.sup.CX3CR1-/-] mice was significantly lower than that in C57BL/6 wild-type mice (4.36% [+ or -] 1.27% vs. 12.17% [+ or -] 3.81%, p < 0.001). The survival rate of [C57BL/6.sup.CX3CR1-/-] mice (25%) was significantly lower than that of C57BL/6 wild-type mice (56.3%) after AMI ([chi square] = 4.343, p = 0.037). After MSCs were transplanted, we observed a significant increase in [Ly6C.sup.low] monocytes both in circulation (16.7% [+ or -] 3.67% vs. 3.22% [+ or -] 0.44%, p < 0.001) and in the MI heart (3.31% [+ or -] 0.69% vs. 0.42% [+ or -] 0.21%, p