MicroRNA-19a-3p inhibits endothelial dysfunction in atherosclerosis by targeting JCAD

  • BMC Cardiovasc Disord. 2024 Jul 30;24(1):394. doi: 10.1186/s12872-024-04063-y.
Jinque Luo  #  1  2 ,  Ling Wang  #  1  2 ,  Chaoyue Cui  1 ,  Hongyu Chen  1 ,  Wanli Zeng  1 ,  Xin Li  3
Affiliations
  • 1. Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, "The 14th Five-Year Plan" Application Characteristic Discipline of Hunan Province (Pharmaceutical Science), College of Pharmacy, Changsha Medical University, 1501 Leifeng Avenue, Changsha, 410219, Hunan, China.
  • 2. College of Pharmacy, Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Functional Nucleic Acid, Changsha Medical University, Changsha, 410219, Hunan, China.
  • 3. Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, "The 14th Five-Year Plan" Application Characteristic Discipline of Hunan Province (Pharmaceutical Science), College of Pharmacy, Changsha Medical University, 1501 Leifeng Avenue, Changsha, 410219, Hunan, China. [email protected].
  • # Contributed equally.
PMID: 39080547 DOI: 10.1186/s12872-024-04063-y
Abstract

Objective: To examine the influences and mechanisms of MicroRNA-19a-3p (miR-19a-3p) on endothelial dysfunction in Atherosclerosis.

Methods: An analysis of miR-19a expression was carried out using the Gene Expression Omnibus (GEO) database. The effect of miR-19a-3p on endothelial function in HUVECs was evaluated by miR-19a-3p overexpression under TNF-α treatment. Luciferase assays were performed to explore the potential target genes. Overexpression of junctional protein associated with coronary artery disease (JCAD) was used to examine the effects of miR-19a-3p on cell adhesion, and proliferation.

Results: MiR-19a-3p expression in endothelial cells decreased after exposure to TNF-α and/or oscillatory flow, consistent with the expression change of miR-19a-3p found in atherosclerotic plaques. Additionally, endothelial cell dysfunction and inflammation were significantly diminished by miR-19a-3p overexpression but markedly exacerbated by miR-19a-3p inhibition. MiR-19a-3p transfection significantly decreased the expression of JCAD by binding to the 3'-UTR of JCAD mRNA. Furthermore, the protective effect of miR-19a-3p against endothelial cell dysfunction and inflammation was achieved by regulating JCAD and was closely linked to the Hippo/YAP signaling pathway.

Conclusion: MiR-19a-3p expression is a crucial molecular switch in the onset of Atherosclerosis and miR-19a-3p overexpression is a possible pharmacological therapeutic strategy for reversing the development of Atherosclerosis.

Keywords
Atherosclerosis; Endothelial dysfunction; Inflammation; JCAD; MicroRNA-19a-3p.
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