Pathophysiological understanding of HFpEF: microRNAs as part of the puzzle

Monika Rech, Arantxa Barandiaran Aizpurua, Vanessa van Empel, Marc van Bilsen, Blanche Schroen*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

31 Citations (Web of Science)

Abstract

Half of all heart failure patients have preserved ejection fraction (HFpEF). Comorbidities associated with and contributing to HFpEF include obesity, diabetes and hypertension. Still, the underlying pathophysiological mechanisms of HFpEF are unknown. A preliminary consensus proposes that the multi-morbidity triggers a state of systemic, chronic low-grade inflammation, and microvascular dysfunction, causing reduced nitric oxide bioavailability to adjacent cardiomyocytes. As a result, the cardiomyocyte remodels its contractile elements and fails to relax properly, causing diastolic dysfunction, and eventually HFpEF. HFpEF is a complex syndrome for which currently no efficient therapies exist. This is notably due to the current one-size-fits-all therapy approach that ignores individual patient differences. MicroRNAs have been studied in relation to pathophysiological mechanisms and comorbidities underlying and contributing to HFpEF. As regulators of gene expression, microRNAs may contribute to the pathophysiology of HFpEF. In addition, secreted circulating microRNAs are potential biomarkers and as such, they could help stratify the HFpEF population and open new ways for individualized therapies. In this review, we provide an overview of the ever-expanding world of non-coding RNAs and their contribution to the molecular mechanisms underlying HFpEF. We propose prospects for microRNAs in stratifying the HFpEF population. MicroRNAs add a new level of complexity to the regulatory network controlling cardiac function and hence the understanding of gene regulation becomes a fundamental piece in solving the HFpEF puzzle.
Original languageEnglish
Pages (from-to)782-793
Number of pages12
JournalCardiovascular Research
Volume114
Issue number6
DOIs
Publication statusPublished - 1 May 2018

Keywords

  • Heart
  • HFpEF
  • MicroRNA
  • PRESERVED EJECTION FRACTION
  • INDUCED CARDIAC-HYPERTROPHY
  • HIGH-FAT DIET
  • HEART-FAILURE
  • MICROVASCULAR DYSFUNCTION
  • ENDOTHELIAL DYSFUNCTION
  • DILATED CARDIOMYOPATHY
  • CIRCULATING MICRORNAS
  • INSULIN SENSITIVITY
  • GLUCOSE-METABOLISM

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