Cell-based mechanosensation, epigenetics, and non-coding RNAs in progression of cardiac fibrosis

Research output: Contribution to journalReview article

Abstract

The heart is par excellence the ‘in-motion’ organ in the human body. Compelling evidence shows that, besides generating forces to ensure continuous blood supply (e.g., myocardial contractility) or withstanding passive forces generated by flow (e.g., shear stress on endocardium, myocardial wall strain, and compression strain at the level of cardiac valves), cells resident in the heart respond to mechanical cues with the activation of mechanically dependent molecular pathways. Cardiac stromal cells, most commonly named cardiac fibroblasts, are central in the pathologic evolution of the cardiovascular system. In their normal function, these cells translate mechanical cues into signals that are necessary to renew the tissues, e.g., by continuously rebuilding the extracellular matrix being subjected to mechanical stress. In the presence of tissue insults (e.g., ischemia), inflammatory cues, or modifiable/unmodifiable risk conditions, these mechanical signals may be ‘misinterpreted’ by cardiac fibroblasts, giving rise to pathology programming. In fact, these cells are subject to changing their phenotype from that of matrix renewing to that of matrix scarring cells—the so-called myo-fibroblasts—involved in cardiac fibrosis. The links between alterations in the abilities of cardiac fibroblasts to ‘sense’ mechanical cues and molecular pathology programming are still under investigation. On the other hand, various evidence suggests that cell mechanics may control stromal cells phenotype by modifying the epigenetic landscape, and this involves specific non-coding RNAs. In the present contribution, we will provide examples in support of this more integrated vision of cardiac fibrotic progression based on the decryption of mechanical cues in the context of epigenetic and non-coding RNA biology.

Original languageEnglish
Article number28
JournalInternational Journal of Molecular Sciences
Volume21
Issue number1
DOIs
Publication statusPublished - Jan 1 2020

Keywords

  • Cardiac fibroblast
  • Cardiac fibrosis
  • Epigenetics
  • Heart failure
  • Mechanotransduction
  • Non-coding RNAs

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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