Fenofibrate Reverses Dysfunction of EPCs Caused by Chronic Heart Failure

Wen Pin Huang, Wei Hsian Yin, Jia Shiong Chen, Po Hsun Huang, Jaw Wen Chen, Shing Jong Lin

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

The enhanced activity of endothelial progenitor cells (EPCs) by AMP-activated protein kinase (AMPK) agonists might explain the reversal of chronic heart failure (CHF)–mediated endothelial dysfunction. We studied baseline circulating EPC numbers in patients with heart failure and clarified the effect of fenofibrate on both circulating angiogenic cell (CAC) and late EPC activity. The numbers of circulating EPCs in CHF patients were quantified by flow cytometry. Blood-derived mononuclear cells were cultured, and CAC and late EPC functions, including fibronectin adhesion, tube formation, and migration, were evaluated. We focused on the effect of fenofibrate, an AMPK agonist, on EPC function and Akt/eNOS cascade activation in vitro. The number of circulating EPCs (CD34+/KDR+) was significantly lower in CHF patients (ischemic cardiomyopathy (ICMP): 0.07%, dilated cardiomyopathy (DCMP): 0.068%; p < 0.05) than in healthy subjects (0.102% of the gating region). In CACs, fibronectin adhesion function was reversed by fenofibrate treatment (p < 0.05). Similar results were also found for tube formation and migration in late EPCs, which were significantly improved by fenofibrate in an AMPK-dependent manner (p < 0.05), suggesting that fenofibrate reversed CACs and late EPC dysfunction in CHF patients. The present findings reveal the potential application of the AMPK agonist fenofibrate to reverse endothelial dysfunction in CHF patients.

Original languageEnglish
Pages (from-to)158-170
Number of pages13
JournalJournal of Cardiovascular Translational Research
Volume13
Issue number2
DOIs
Publication statusPublished - Apr 1 2020
Externally publishedYes

Keywords

  • AMPK
  • Chronic heart failure
  • Endothelial progenitor cell
  • eNOS
  • Fenofibrate

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmaceutical Science
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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