C2238/αANP modulates apolipoprotein E through Egr-1/miR199a in vascular smooth muscle cells in vitro.

摘要: Subjects carrying the T2238C ANP gene variant have a higher risk to suffer stroke or myocardial infarction. The mechanisms through which T2238C/αANP exerts detrimental vascular effects need be fully clarified. In present work we aimed at exploring impact of C2238/αANP (mutant form) on atherosclerosis-related pathways. As first step, an atherosclerosis expression macroarray analysis was performed in smooth muscle cells (VSMCs) exposed either T2238/αANP (wild type) C2238/αANP. major finding that apolipoprotein E (ApoE) significantly downregulated by and it upregulated T2238/αANP. We subsequently found induces ApoE downregulation type C natriuretic peptide receptor (NPR-C)-dependent involving upregulation miR199a-3p miR199a-5p DNAJA4. fact, NPR-C knockdown rescued level. Upregulation miR199a mediated reactive oxygen species-dependent increase early growth response protein-1 (Egr-1) transcription factor. Egr-1 abolished miR199a. Of note, associated with significant inflammation, apoptosis necrosis completely exogenous administration recombinant ApoE. conclusion, our study dissected novel mechanism damage exerted is downregulation. provide demonstration downregulates VSMCs NPR-C-dependent activation consequent Restoring levels could represent potential therapeutic strategy counteract harmful