PMID- 30474386 OWN - NLM STAT- MEDLINE DCOM- 20200205 LR - 20211204 IS - 1940-4034 (Electronic) IS - 1074-2484 (Linking) VI - 24 IP - 3 DP - 2019 May TI - Employing the Sirolimus-Eluting Poly (Propylene Carbonate) Mesh for the Prevention of Arteriovenous Graft Stenosis in Rats. PG - 269-277 LID - 10.1177/1074248418806060 [doi] AB - Poly (propylene carbonate, PPC) is a new member of the aliphatic polyester family. An outstanding feature of PPC is that it produces mainly water and carbon dioxide when degraded in vivo, causing minimal side effects. This unique property together with excellent biocompatibility and biodegradability makes PPC a promising material for drug delivery. In this study, we explored the effect of the sirolimus (an inhibitor of cell growth)-eluting PPC mesh on graft stenosis and its possible mechanisms in a rat arteriovenous grafting model. The PPC mesh was prepared by electrospinning. A jugular vein to abdominal aortic autograft transplantation model was established in rats. The graft was then treated by wrapping with the drug mesh or the drug-free mesh or left untreated. Four weeks posttransplantation, neointima was measured with hematoxylin and eosin staining, matrix metalloproteinase-2 (MMP-2), and MMP-9, and proliferating cell nuclear antigen (PCNA) in the grafts were assayed by Western blotting and immunohistochemistry, respectively. In vitro rat aortic adventitial fibroblast cell (RAAFC) migration was assessed using the Boyden chamber assay, and phospho-mammalian target of rapamycin (mTOR) levels in RAAFCs were determined by Western blotting. Animals with the drug mesh had an intimal area index of 4.87% +/- 0.98%, significantly lower than that of the blank group (14.21% +/- 2.56%) or the PPC group (15.03% +/- 2.35%, both P < .05). The sirolimus mesh markedly suppressed MMP-2 and MMP-9 expression, decreased PCNA-positive cell numbers, inhibited RAAFC migration, and reduced phospho-mTOR levels. Our data suggest that the sirolimus-eluting PPC mesh might be potentially applied for the management of grafting stenosis. FAU - Sun, Hourong AU - Sun H AD - 1 Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China. FAU - Liu, Chuan-Zhen AU - Liu CZ AD - 1 Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China. FAU - Liu, Chunxiao AU - Liu C AD - 1 Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China. FAU - Tang, Mengmeng AU - Tang M AD - 1 Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China. FAU - Cao, Guangqing AU - Cao G AD - 1 Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China. FAU - Zhang, Qiuwang AU - Zhang Q AD - 2 Division of Cardiology, Keenan Research Center for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. FAU - Gu, Xinghua AU - Gu X AUID- ORCID: 0000-0003-2175-6870 AD - 1 Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181126 PL - United States TA - J Cardiovasc Pharmacol Ther JT - Journal of cardiovascular pharmacology and therapeutics JID - 9602617 RN - 0 (Cardiovascular Agents) RN - 0 (Coated Materials, Biocompatible) RN - 0 (Proliferating Cell Nuclear Antigen) RN - 8D08K3S51E (propylene carbonate) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.24 (Mmp2 protein, rat) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - EC 3.4.24.35 (Mmp9 protein, rat) RN - T75W9911L6 (Propane) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Animals MH - Aorta, Abdominal/*surgery MH - Autografts MH - Cardiovascular Agents/*administration & dosage MH - Cell Movement MH - *Coated Materials, Biocompatible MH - Equipment Design MH - Fibroblasts/metabolism/pathology MH - Graft Occlusion, Vascular/metabolism/pathology/physiopathology/*prevention & control MH - Jugular Veins/metabolism/pathology/physiopathology/*transplantation MH - Male MH - Matrix Metalloproteinase 2/metabolism MH - Matrix Metalloproteinase 9/metabolism MH - Phosphorylation MH - Proliferating Cell Nuclear Antigen/metabolism MH - Propane/*analogs & derivatives MH - Rats, Wistar MH - Sirolimus/*administration & dosage MH - *Surgical Mesh MH - TOR Serine-Threonine Kinases/metabolism MH - Vascular Grafting/adverse effects/*instrumentation MH - Vascular Patency OTO - NOTNLM OT - arteriovenous grafting OT - cell migration OT - intimal hyperplasia OT - matrix metalloproteinase OT - poly (propylene carbonate) OT - sirolimus OT - stenosis EDAT- 2018/11/27 06:00 MHDA- 2020/02/06 06:00 CRDT- 2018/11/27 06:00 PHST- 2018/11/27 06:00 [pubmed] PHST- 2020/02/06 06:00 [medline] PHST- 2018/11/27 06:00 [entrez] AID - 10.1177/1074248418806060 [doi] PST - ppublish SO - J Cardiovasc Pharmacol Ther. 2019 May;24(3):269-277. doi: 10.1177/1074248418806060. Epub 2018 Nov 26.