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Citronellal can alleviate vascular endothelial dysfunction by reducing ectopic miR-133a expression.

Yue Qiu1, Xue Zhang2, Shan-Shan Li2

  • 1Department of Pharmacy, Beijing Renhe Hospital, Beijing 102600, China; Sino-UK Joint Laboratory of Brain Function and Injury and Department of Physiology and Neurobiology, Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention, School of Basic Medical Sciences, College of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China.

Life Sciences
|December 28, 2023
PubMed
Summary

Citronellal (CT) effectively reduces atherosclerosis by improving endothelial function. It enhances AP-2α and circRNA_102979 expression, counteracting miR-133a inhibition and alleviating endothelial dysfunction in cardiovascular disease models.

Keywords:
AP-2αCitronellalEndothelial dysfunctioncircRNA-102979miR-133a

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Area of Science:

  • Cardiovascular Research
  • Molecular Biology
  • Natural Product Chemistry

Background:

  • Endothelial dysfunction (ED) is a primary driver of atherosclerosis (AS) and an early indicator of cardiovascular diseases (CVD).
  • Citronellal (CT), a natural monoterpenoid from Citronella, exhibits known anti-thrombotic, anti-hypertensive, and anti-diabetic effects.
  • Investigating CT's role in vascular health is crucial for developing novel therapeutic strategies.

Purpose of the Study:

  • To elucidate the therapeutic effects of Citronellal (CT) on vascular endothelial dysfunction.
  • To explore the underlying molecular mechanisms by which CT influences atherosclerosis progression.

Main Methods:

  • AS and ED models were established in mice using balloon injury and high-fat diet, alongside an HUVEC oxidative stress model.
  • Key molecular changes were assessed using Western blot, RT-PCR, ELISA, and immunohistochemistry.
  • The roles of AP-2α, circRNA_102979, and miR-133a were investigated using silencing techniques.

Main Results:

  • CT significantly reduced atherosclerotic plaque area and lipid deposition in a dose-dependent manner.
  • CT upregulated AP-2α (TFAP2A) and circRNA_102979 expression while downregulating miR-133a.
  • Silencing AP-2α or circRNA_102979 reversed the protective effects of CT.

Conclusions:

  • Citronellal (CT) ameliorates atherosclerosis-induced endothelial dysfunction.
  • CT enhances AP-2α and circRNA_102979 expression, promoting circRNA_102979's sequestration of miR-133a.
  • This mechanism alleviates miR-133a's inhibitory impact on target genes, offering a novel therapeutic pathway for ED and AS.