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Molecular Medicine

, Volume 21, Issue 1, pp 616–625 | Cite as

Angiotensin II Downregulates MicroRNA-145 to Regulate Kruppel-like Factor 4 and Myocardin Expression in Human Coronary Arterial Smooth Muscle Cells under High Glucose Conditions

  • Kou-Gi Shyu
  • Wen-Ping Cheng
  • Bao-Wei Wang
Research Article

Abstract

MicroRNA (miR)-145 is the most abundant miR in vascular smooth muscle cells (VSMCs). However, the effect of hyperglycemia on the regulation of miR-145 is unknown. We hypothesized that the hyperglycemic condition activates a proinflammatory response that mediates the expression of miR-145 in VSMCs. We investigated whether miR-145 serves as a critical regulator to regulate the downstream proliferation factors (including Kruppel-like factor 4 (Klf4) and myocardin) in VSMCs under hyperglycemic conditions. Human coronary artery smooth muscle cells (HCASMCs) were cultured under high glucose conditions. Sustained high glucose at 25 mmol/L significantly decreased the expression of miR-145 in HCASMCs. High glucose significantly increased angiotensin II (Ang II) secretion from HCASMCs and Ang II suppressed miR-145 expression in HCASMCs. Ang II repression of miR145 expression resulted in increased Klf4 and decreased myocardin expression under conditions of high glucose. Overexpression of miR-145 significantly decreased Klf4 and increased myocardin expression and inhibited HCASMC proliferation and migration induced by a high glucose state. Balloon injury of the carotid artery in diabetic rats was performed to investigate miR-145, Klf and myocardin expression. The expression of miR-145 was maximally increased at 7 d after carotid injury and gradually declined thereafter. Overexpression of miR-145 and treatment with valsartan reversed Klf4 and myocardin protein expression induced by balloon injury and improved vascular injury. In conclusion, our study reveals that Ang II downregulates miR-145 to regulate Klf4 and myocardin expression in HCASMCs under high glucose conditions. Ang II plays a critical role in the regulation of miR-145 under hyperglycemic conditions.

Notes

Acknowledgments

This study was supported by grants from Ministry of Science and Technology, Taiwan and Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.

Supplementary material

10020_2015_2101616_MOESM1_ESM.pdf (2.9 mb)
Supplementary material, approximately 2.88 MB.

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Authors and Affiliations

  1. 1.Division of CardiologyShin Kong Wu Ho-Su Memorial HospitalTaipeiTaiwan
  2. 2.Graduate Institute of Clinical MedicineTaipei Medical UniversityTaipeiTaiwan
  3. 3.Department of Medical Education and ResearchShin Kong Wu Ho-Su Memorial HospitalTaipeiTaiwan

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