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The antagonistic effects and mechanisms of microRNA-26a action in hypertensive vascular remodeling
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  • Wenqian Zhang,
  • Qiaozhu Wang,
  • Xin Xing,
  • Lijun Yang,
  • Min Xu,
  • Chunhui Cao,
  • Rong Wang,
  • Weicheng Li,
  • Xiaolin Niu,
  • Dengfeng Gao
Wenqian Zhang
Xi'an Jiaotong University Second Affiliated Hospital
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Qiaozhu Wang
Xi'an Jiaotong University Second Affiliated Hospital
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Xin Xing
Xi'an Jiaotong University Second Affiliated Hospital
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Lijun Yang
Xi'an Jiaotong University Second Affiliated Hospital
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Min Xu
Xi'an Jiaotong University Second Affiliated Hospital
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Chunhui Cao
Xi'an Jiaotong University Second Affiliated Hospital
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Rong Wang
Xi'an Jiaotong University Second Affiliated Hospital
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Weicheng Li
Xi'an Jiaotong University Second Affiliated Hospital
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Xiaolin Niu
Xi'an Jiaotong University Second Affiliated Hospital
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Dengfeng Gao
2nd affiliated hospital of Xi'an Jiaotong University
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Abstract

Background and Purpose: Hypertensive vascular remodeling (VR) is responsible for end-organ damage and is the result of increased extracellular matrix accumulation and excessive vascular smooth muscle cell (VSMC) proliferation. MicroRNA-26a (miR-26a), a non-coding small RNA, is involved in multiple cardiovascular diseases. We aimed to validate the effect and mechanisms of miR-26a in hypertensive VR. Experimental Approach: Spontaneously hypertensive rats (SHRs) were injected intravenously with recombinant adeno-associated virus-miR-26a. In vitro experiments, angiotensin II (AngII)-induced VSMCs were transfected with miR-26a mimic or inhibitor. Key Results: We found miR-26a downregulated in the thoracic aorta and plasma of SHRs. Overexpression of miR-26a inhibited extracellular matrix deposition by targeting connective tissue growth factor (CTGF) and mitigated VSMC proliferation by regulating the enhancer of zeste homolog 2 (EZH2)/p21 pathway both in vitro and in vivo. AngII-mediated Smad3 activation suppressed miR-26a expression, which in turn promoted Smad3 activation via targeted regulation of Smad4, leading to further downregulation of miR-26a. Conclusion and Implications: Our study reveals that AngII stimulates a Smads/miR-26a positive feedback loop, which further reduces miR-26a expression, leading to collagen production and VSMC proliferation and consequently, VR. MiR-26a has an antagonistic effect on hypertensive VR and can be a strategy for treating hypertensive VR.

Peer review status:UNDER REVIEW

27 Jul 2020Submitted to British Journal of Pharmacology
30 Jul 2020Assigned to Editor
30 Jul 2020Submission Checks Completed
07 Aug 2020Reviewer(s) Assigned