MiRNA profiling revealed enhanced susceptibility to oxidative stress of endothelial cells from bicuspid aortic valve

Research output: Contribution to journalArticle

Abstract

Aims: Calcific aortic valve stenosis (CAVS)is the most frequent manifestation of aortic valve disease and the third leading cause of cardiovascular disease in the Western countries associated with significant morbidity and mortality. An active biological progression involving inflammation and oxidation leading to valve endothelial damage is considered a hallmark of the early stages of valve degeneration. However, tricuspid (TAV)and bicuspid (BAV)aortic valve deterioration are considered to differ only by shear stress. We hypothesized that endothelial cells (EC)derived from BAV and TAV patients have different miRNA expression patterns and thus distinct pathways could lead to endothelial damage in BAV than TAV patients. Methods and results: We isolated ECs from patients with bicuspid or tricuspid aortic valve, which underwent surgery due to CAVS. MiRNA expression profile by PCR revealed eight upregulated miRNAs between BAV and TAV ECs. Functional analysis identified that BAV ECs presented altered cellular response to oxidative stress and DNA damage stimulus via p53 and alteration in the intrinsic apoptotic signaling pathway. GPX3 and SRXN1 mRNA were express at lower levels in BAV compared to TAV ECs, leading to an increment of DNA double-strand breaks. BAV ECs had a sustained apoptosis activation when compared to TAV ECs. This difference was exacerbated by oxidative stress stimulus leading to a reduced survival rate but completely reverted by miR-328-3p inhibition. Conclusion: The present data showed molecular differences in oxidative stress susceptibility, DNA damage magnitude, and apoptosis induction between ECs derived from BAV and TAV patients.

Original languageEnglish
Pages (from-to)146-154
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume131
DOIs
Publication statusPublished - Jun 2019

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Keywords

  • Apoptosis
  • Bicuspid aortic valve
  • Calcific aortic valve stenosis
  • Endothelial cells
  • Oxidative stress
  • Tricuspid aortic valve

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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