Felix Jansen1, Andreas Zietzer2, Tobias Stumpf2, Anna Flender2, Theresa Schmitz2, Georg Nickenig2, Nikos Werner3. 1. Department of Internal Medicine II, Rheinische Friedrich-Wilhelms University, Bonn, Germany. Electronic address: felix.jansen@ukbonn.de. 2. Department of Internal Medicine II, Rheinische Friedrich-Wilhelms University, Bonn, Germany. 3. Department of Internal Medicine II, Rheinische Friedrich-Wilhelms University, Bonn, Germany. Electronic address: nikos.werner@ukbonn.de.
Abstract
BACKGROUND: Endothelial microparticles (EMPs) inhibit vascular remodeling by transferring functional microRNA (miRNA) into target vascular smooth muscle cells (VSMCs). Because EMPs are increased in diabetic patients and potentially linked to vascular complications in diabetes mellitus, we sought to determine whether effects of EMPs generated under high glucose concentration on vascular remodeling might differ from EMPs derived from untreated cells. METHODS AND RESULTS: EMPs were generated from human coronary endothelial cells (HCAEC) exposed to high glucose concentrations in order to mimic diabetic conditions. These EMPs were defined as 'hyperglycaemic' EMPs (hgEMPs) and their miRNA transfer capacity and functional effects were compared with EMPs generated from 'healthy' untreated HCAECs. In vitro, the intercellular transfer of antiproliferative miRNA-126-3p from ECs to VSMCs via EMPs was significantly reduced under hyperglycaemic conditions. Additionally, EMP-mediated inhibition of the miRNA-126-3p target LRP6 and of VSMC migration and proliferation was abrogated, when hgEMPs were used. In vivo, the inhibitory effect of EMPs on neointima formation, VSMC proliferation and macrophage infiltration was abolished in mice treated with hgEMPs. CONCLUSION: Pathological hyperglycaemic conditions weaken potentially protective intercellular communication mechanisms by affecting EMP content and function.
BACKGROUND: Endothelial microparticles (EMPs) inhibit vascular remodeling by transferring functional microRNA (miRNA) into target vascular smooth muscle cells (VSMCs). Because EMPs are increased in diabeticpatients and potentially linked to vascular complications in diabetes mellitus, we sought to determine whether effects of EMPs generated under high glucose concentration on vascular remodeling might differ from EMPs derived from untreated cells. METHODS AND RESULTS: EMPs were generated from human coronary endothelial cells (HCAEC) exposed to high glucose concentrations in order to mimic diabetic conditions. These EMPs were defined as 'hyperglycaemic' EMPs (hgEMPs) and their miRNA transfer capacity and functional effects were compared with EMPs generated from 'healthy' untreated HCAECs. In vitro, the intercellular transfer of antiproliferative miRNA-126-3p from ECs to VSMCs via EMPs was significantly reduced under hyperglycaemic conditions. Additionally, EMP-mediated inhibition of the miRNA-126-3p target LRP6 and of VSMC migration and proliferation was abrogated, when hgEMPs were used. In vivo, the inhibitory effect of EMPs on neointima formation, VSMC proliferation and macrophage infiltration was abolished in mice treated with hgEMPs. CONCLUSION: Pathological hyperglycaemic conditions weaken potentially protective intercellular communication mechanisms by affecting EMP content and function.
Authors: Andreas Zietzer; Mohammed Rabiul Hosen; Han Wang; Philip Roger Goody; Marc Sylvester; Eicke Latz; Georg Nickenig; Nikos Werner; Felix Jansen Journal: J Extracell Vesicles Date: 2020-07-02
Authors: Andreas Zietzer; Alina Lisann Jahnel; Marko Bulic; Katharina Gutbrod; Philip Düsing; Mohammed Rabiul Hosen; Peter Dörmann; Nikos Werner; Georg Nickenig; Felix Jansen Journal: Cell Mol Life Sci Date: 2021-12-24 Impact factor: 9.261