PMID- 28839206 OWN - NLM STAT- MEDLINE DCOM- 20190411 LR - 20190411 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 IP - 1 DP - 2017 Aug 24 TI - Grape-seed Polyphenols Play a Protective Role in Elastase-induced Abdominal Aortic Aneurysm in Mice. PG - 9402 LID - 10.1038/s41598-017-09674-4 [doi] LID - 9402 AB - Abdominal aortic aneurysm (AAA) is a kind of disease characterized by aortic dilation, whose pathogenesis is linked to inflammation. This study aimed to determine whether grape-seed polyphenols (GSP) has anti-AAA effects and what mechanism is involved, thus to find a way to prevent occurrence and inhibit expansion of small AAA. In our study, AAA was induced by incubating the abdominal aorta of the mice with elastase, and GSP was administrated to the mice by gavage at different doses beginning on the day of the AAA inducement. In in vivo experiments, 800 mg/kg GSP could significantly reduce the incidence of AAA, the dilatation of aorta and elastin degradation in media, and dramatically decrease macrophage infiltration and activation and expression of matrix metalloproteinase (MMP) -2 and MMP-9 in the aorta, compared to the AAA model group. Meanwhile, 400 mg/kg GSP could also but not completely inhibit the occurrence and development of AAA. In in vitro experiments, GSP dose-dependently inhibited mRNA expression of interleukin (IL)-1beta, IL-6 and monocyte chemoattractant protein-1 (MCP-1), and significantly inhibited expression and activity of MMP-2 and MMP-9, thus prevented elastin from degradation. In conclusion, GSP showed great anti-AAA effects and its mechanisms were related to inhibition of inflammation. FAU - Wang, Chao AU - Wang C AD - Peking University Institute of Cardiovascular Sciences, Peking University Health Science Center, Peking University, Beijing, 100191, China. AD - Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, China. AD - Second School of Clinical Medicine, Peking University, Beijing, 100044, China. FAU - Wang, Yunxia AU - Wang Y AD - Peking University Institute of Cardiovascular Sciences, Peking University Health Science Center, Peking University, Beijing, 100191, China. AD - Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, China. AD - Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Beijing, 100191, China. FAU - Yu, Maomao AU - Yu M AD - Peking University Institute of Cardiovascular Sciences, Peking University Health Science Center, Peking University, Beijing, 100191, China. AD - Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, China. FAU - Chen, Cong AU - Chen C AD - Peking University Institute of Cardiovascular Sciences, Peking University Health Science Center, Peking University, Beijing, 100191, China. AD - Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, China. AD - Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Beijing, 100191, China. FAU - Xu, Lu AU - Xu L AD - Peking University Institute of Cardiovascular Sciences, Peking University Health Science Center, Peking University, Beijing, 100191, China. AD - Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, China. FAU - Cao, Yini AU - Cao Y AD - Peking University Institute of Cardiovascular Sciences, Peking University Health Science Center, Peking University, Beijing, 100191, China. AD - Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, China. AD - Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Beijing, 100191, China. FAU - Qi, Rong AU - Qi R AD - Peking University Institute of Cardiovascular Sciences, Peking University Health Science Center, Peking University, Beijing, 100191, China. ronaqi@bjmu.edu.cn. AD - Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, China. ronaqi@bjmu.edu.cn. AD - Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Beijing, 100191, China. ronaqi@bjmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170824 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Plant Extracts) RN - 0 (Polyphenols) RN - 0 (Protective Agents) RN - EC 3.4.21.36 (Pancreatic Elastase) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Animals MH - Aortic Aneurysm, Abdominal/drug therapy/*etiology/*pathology/prevention & control MH - Biomarkers MH - Biopsy MH - Cytokines/metabolism MH - Disease Models, Animal MH - Gene Expression MH - Inflammation/pathology MH - Inflammation Mediators/metabolism MH - Matrix Metalloproteinase 2/genetics/metabolism MH - Matrix Metalloproteinase 9/genetics/metabolism MH - Mice MH - Mice, Knockout MH - Muscle, Smooth, Vascular/cytology/metabolism MH - Myocytes, Smooth Muscle/metabolism/pathology MH - Pancreatic Elastase/deficiency MH - Plant Extracts/chemistry/*pharmacology MH - Polyphenols/chemistry/*pharmacology MH - Protective Agents/chemistry/*pharmacology MH - Seeds/*chemistry MH - Vitis/*chemistry PMC - PMC5570906 COIS- The authors declare that they have no competing interests. EDAT- 2017/08/26 06:00 MHDA- 2019/04/12 06:00 PMCR- 2017/08/24 CRDT- 2017/08/26 06:00 PHST- 2017/01/03 00:00 [received] PHST- 2017/07/14 00:00 [accepted] PHST- 2017/08/26 06:00 [entrez] PHST- 2017/08/26 06:00 [pubmed] PHST- 2019/04/12 06:00 [medline] PHST- 2017/08/24 00:00 [pmc-release] AID - 10.1038/s41598-017-09674-4 [pii] AID - 9674 [pii] AID - 10.1038/s41598-017-09674-4 [doi] PST - epublish SO - Sci Rep. 2017 Aug 24;7(1):9402. doi: 10.1038/s41598-017-09674-4.