caa a22 4500 606158286 CHVBK 20210128100618.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s10557-014-6561-6 doi (NATIONALLICENCE)springer-10.1007/s10557-014-6561-6 The ADP Antagonist MRS2179 Regulates the Phenotype of Smooth Muscle Cells to Limit Intimal Hyperplasia [Elektronische Daten] [Rong Liu, Shixin Ma, Zhigang Lu, Hong Shen, Leiqing Sun, Meng Wei] Purpose: ADP plays an important part in platelet aggregation by activating P2Y1 and P2Y12 receptors. The ADP antagonist MRS2179 has been used in thrombosis-related treatments but its effects on vein graft (VG) remodeling is undefined. We examined the effect of MRS2179 on VG intimal hyperplasia and explored the mechanism of action. Methods: A mouse model of VG transplantation was established. Mice underwent surgery and received MRS2179 by intraperitoneal injection every other day for 3weeks. VG remodeling was assessed 4-weeks later. Vascular smooth muscle cells (VSMCs) were isolated and treated with MRS2179. The effect of MRS2179 on the proliferation, migration and inflammatory-cytokine expression of VSMCs was also evaluated. Results: MRS2179 significantly inhibited VSMC proliferation compared with the control group. Significant inhibitory effects of MRS2179 on VSMC migration was observed in two-dimensional and three-dimensional models. The extent of intimal hyperplasia was significantly less in MRS2179 treated mice than in controls. Reduced migration of macrophage was found in MRS2179 treated mice. Expression of the inflammatory cytokines IL-1β and TNF-α was decreased significantly in the MRS2179 treated group. In addition, decreased phosphorylation was found on Akt, Erk1/2 and p38. Conclusions: These data demonstrate that MRS2179 inhibits neointima formation in VGs by regulating the proliferation, and migration of VSMCs, macrophage migration, inflammatory-cytokine secretion and related signaling pathway. Our study provides novel insights regarding purinergic signaling in SMCs in vivo. The P2Y1 receptor may serve as a therapeutic target in neointima formation. Springer Science+Business Media New York, 2014 MRS2179 nationallicence Vein graft nationallicence Vascular smooth muscle cells nationallicence Proliferation nationallicence Migration nationallicence Liu Rong Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, 200233, Shanghai, China aut Ma Shixin Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, 200233, Shanghai, China aut Lu Zhigang Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, 200233, Shanghai, China aut Shen Hong Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, 200233, Shanghai, China aut Sun Leiqing Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, 200233, Shanghai, China aut Wei Meng Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, 200233, Shanghai, China aut Cardiovascular Drugs and Therapy Springer US; http://www.springer-ny.com 29/1(2015-02-01), 23-29 0920-3206 29:1<23 2015 29 10557 https://doi.org/10.1007/s10557-014-6561-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10557-014-6561-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Liu Rong Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, 200233, Shanghai, China aut NATIONALLICENCE 700 1- Ma Shixin Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, 200233, Shanghai, China aut NATIONALLICENCE 700 1- Lu Zhigang Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, 200233, Shanghai, China aut NATIONALLICENCE 700 1- Shen Hong Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, 200233, Shanghai, China aut NATIONALLICENCE 700 1- Sun Leiqing Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, 200233, Shanghai, China aut NATIONALLICENCE 700 1- Wei Meng Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, 200233, Shanghai, China aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Springer US; http://www.springer-ny.com 29/1(2015-02-01), 23-29 0920-3206 29:1<23 2015 29 10557