BACKGROUND: Dysregulated microRNAs are involved in the macrophage polarization and atherosclerotic development. Apart from microRNAs, alteration in DNA methylation is considered as one of the most frequent epigenetic changes. The purpose of the research is to investigate the altered methylation status of miR-181b in the circulating monocytes from patients with coronary artery disease (CAD) and explore the underlying mechanisms. METHODS: We examined the methylation status of miR-181b in purified circulating monocytes from patients with CAD and healthy controls. We then transfected monocytes with miR-181b mimics and determined the role of miR-181b on the phenotypic switch of macrophages and inflammatory response. DNA methylation levels determined by MethyLight PCR and pyrosequencing at the promoter of miR-181b significantly increased in CAD patients. Based on TargetScan database, we identified PIAS1 as the target gene of miR-181b and explored the interaction of miR-181b and PIAS1 by Dual-Luciferase assay, quantitative PCR and immunoblots. We also investigated the role of miR-181b and PIAS1 on macrophage polarization and inflammation. RESULTS: Hypermethylation at the promoter of miR-181b directly contributed to the decrease of miR-181b activity and expression. Overexpression of miR-181b reduced M1 polarization and facilitated M2 polarization determined by quantitative PCR. While knockdown of PIAS1 induced KLF4 degradation and SUMOylation in monocytes, miR-181b mimics reverse the KLF4 SUMOylation via suppression of PIAS1. Moreover, KLF4 SUMOylation by PIAS1 reversed M1 polarization induced by depletion of miR-181b in monocytes. CONCLUSIONS: Hypermethylation of miR-181b induces M1 polarization and promotes atherosclerosis through activation of PIAS1 and KLF4 SUMOylation in macrophages. 2020 Cardiovascular Diagnosis and Therapy. All rights reserved.
BACKGROUND: Dysregulated microRNAs are involved in the macrophage polarization and atherosclerotic development. Apart from microRNAs, alteration in DNA methylation is considered as one of the most frequent epigenetic changes. The purpose of the research is to investigate the altered methylation status of miR-181b in the circulating monocytes from patients with coronary artery disease (CAD) and explore the underlying mechanisms. METHODS: We examined the methylation status of miR-181b in purified circulating monocytes from patients with CAD and healthy controls. We then transfected monocytes with miR-181b mimics and determined the role of miR-181b on the phenotypic switch of macrophages and inflammatory response. DNA methylation levels determined by MethyLight PCR and pyrosequencing at the promoter of miR-181b significantly increased in CAD patients. Based on TargetScan database, we identified PIAS1 as the target gene of miR-181b and explored the interaction of miR-181b and PIAS1 by Dual-Luciferase assay, quantitative PCR and immunoblots. We also investigated the role of miR-181b and PIAS1 on macrophage polarization and inflammation. RESULTS: Hypermethylation at the promoter of miR-181b directly contributed to the decrease of miR-181b activity and expression. Overexpression of miR-181b reduced M1 polarization and facilitated M2 polarization determined by quantitative PCR. While knockdown of PIAS1 induced KLF4 degradation and SUMOylation in monocytes, miR-181b mimics reverse the KLF4 SUMOylation via suppression of PIAS1. Moreover, KLF4 SUMOylation by PIAS1 reversed M1 polarization induced by depletion of miR-181b in monocytes. CONCLUSIONS: Hypermethylation of miR-181b induces M1 polarization and promotes atherosclerosis through activation of PIAS1 and KLF4 SUMOylation in macrophages. 2020 Cardiovascular Diagnosis and Therapy. All rights reserved.
Authors: Márton Kolossváry; Bálint Szilveszter; István Ferenc Édes; Sándor Nardai; Viktor Voros; István Hartyánszky; Béla Merkely; Szilard Voros; Pál Maurovich-Horvat Journal: Am J Cardiol Date: 2016-04-05 Impact factor: 2.778
Authors: Clinton S Robbins; Ingo Hilgendorf; Georg F Weber; Igor Theurl; Yoshiko Iwamoto; Jose-Luiz Figueiredo; Rostic Gorbatov; Galina K Sukhova; Louisa M S Gerhardt; David Smyth; Caleb C J Zavitz; Eric A Shikatani; Michael Parsons; Nico van Rooijen; Herbert Y Lin; Mansoor Husain; Peter Libby; Matthias Nahrendorf; Ralph Weissleder; Filip K Swirski Journal: Nat Med Date: 2013-08-11 Impact factor: 53.440
Authors: Severi Mulari; Arda Eskin; Milla Lampinen; Annu Nummi; Tuomo Nieminen; Kari Teittinen; Teija Ojala; Matti Kankainen; Antti Vento; Jari Laurikka; Markku Kupari; Ari Harjula; Nurcan Tuncbag; Esko Kankuri Journal: Front Cardiovasc Med Date: 2021-12-02