Heart failure with preserved ejection fraction: molecular pathways of the aging myocardium

Circ Res. 2014 Jun 20;115(1):97-107. doi: 10.1161/CIRCRESAHA.115.302929.

Abstract

Age-related diastolic dysfunction is a major factor in the epidemic of heart failure. In patients hospitalized with heart failure, HFpEF is now as common as heart failure with reduced ejection fraction. We now have many successful treatments for heart failure with reduced ejection fraction, while specific treatment options for HFpEF patients remain elusive. The lack of treatments for HFpEF reflects our very incomplete understanding of this constellation of diseases. There are many pathophysiological factors in HFpEF, but aging appears to play an important role. Here, we propose that aging of the myocardium is itself a specific pathophysiological process. New insights into the aging heart, including hormonal controls and specific molecular pathways, such as microRNAs, are pointing to myocardial aging as a potentially reversible process. While the overall process of aging remains mysterious, understanding the molecular pathways of myocardial aging has never been more important. Unraveling these pathways could lead to new therapies for the enormous and growing problem of HFpEF.

Keywords: aging; diastolic dysfunction; heart failure, diastolic.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aging / physiology*
  • Calcium Signaling
  • Calcium-Binding Proteins / physiology
  • Cyclic GMP-Dependent Protein Kinases / physiology
  • Diastole
  • Fibrosis
  • Heart Failure / physiopathology*
  • Heart Failure / therapy
  • Humans
  • Intracellular Signaling Peptides and Proteins / physiology
  • Matrix Metalloproteinases / physiology
  • MicroRNAs / physiology
  • Mitochondria / physiology
  • Myocardium / pathology
  • Sirtuins / physiology
  • Stroke Volume / physiology*
  • Telomere

Substances

  • Calcium-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • MicroRNAs
  • RGN protein, human
  • Cyclic GMP-Dependent Protein Kinases
  • Matrix Metalloproteinases
  • SIRT6 protein, human
  • Sirtuins