2. Academic Validation
  3. Endothelial-derived extracellular microRNA-92a promotes arterial stiffness by regulating phenotype changes of vascular smooth muscle cells

Endothelial-derived extracellular microRNA-92a promotes arterial stiffness by regulating phenotype changes of vascular smooth muscle cells

  • Sci Rep. 2022 Jan 10;12(1):344. doi: 10.1038/s41598-021-04341-1.
Chen Wang  # 1 2,  Haoyu Wu  # 1,  Yuanming Xing 1 2,  Yulan Ye 3,  Fangzhou He 2,  Qian Yin 1 2,  Yujin Li 4,  Fenqing Shang 5 6,  John Y-J Shyy 7,  Zu-Yi Yuan 8
Affiliations

Affiliations

  • 1 Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • 2 Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.
  • 3 Department of Cardiology, Xi'an GaoXin Hospital, Xi'an, China.
  • 4 Department of Life Sciences and Medicine, Northwestern University, Xi'an, China.
  • 5 Translational Medicine Centre, Xi'an Chest Hospital, Xi'an, China. shangfenqing@163.com.
  • 6 Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China. shangfenqing@163.com.
  • 7 Division of Cardiology, Department of Medicine, University of California, La Jolla, San Diego, CA, USA.
  • 8 Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. zuyiyuan@mail.xjtu.edu.cn.
  • # Contributed equally.
PMID: 35013491 DOI: 10.1038/s41598-021-04341-1
Abstract

Endothelial dysfunction and vascular smooth muscle cell (VSMC) plasticity are critically involved in the pathogenesis of hypertension and arterial stiffness. MicroRNAs can mediate the cellular communication between vascular endothelial cells (ECs) and neighboring cells. Here, we investigated the role of endothelial-derived extracellular microRNA-92a (miR-92a) in promoting arterial stiffness by regulating EC-VSMC communication. Serum miR-92a level was higher in hypertensive patients than controls. Circulating miR-92a level was positively correlated with pulse wave velocity (PWV), systolic blood pressure (SBP), diastolic blood pressure (DBP), and serum endothelin-1 (ET-1) level, but inversely with serum nitric oxide (NO) level. In vitro, angiotensin II (Ang II)-increased miR-92a level in ECs mediated a contractile-to-synthetic phenotype change of co-cultured VSMCs. In Ang II-infused mice, locked nucleic acid-modified antisense miR-92a (LNA-miR-92a) ameliorated PWV, SBP, DBP, and impaired vasodilation induced by Ang II. LNA-miR-92a administration also reversed the increased levels of proliferative genes and decreased levels of contractile genes induced by Ang II in mouse aortas. Circulating serum miR-92a level and PWV were correlated in these mice. These findings indicate that EC miR-92a may be transported to VSMCs via extracellular vesicles to regulate phenotype changes of VSMCs, leading to arterial stiffness.

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