Impaired endothelial function contributes to cardiac dysfunction: role of mitochondrial dynamics

Am J Physiol Heart Circ Physiol. 2025 Jan 1;328(1):H29-H36. doi: 10.1152/ajpheart.00531.2024. Epub 2024 Nov 19.

Abstract

The endothelial microvasculature is essential for the regulation of vasodilation and vasoconstriction, and improved functioning of the endothelium is linked to improved outcomes for individuals with coronary artery disease (CAD). People with endothelial dysfunction exhibit a loss of nitric oxide (NO)-mediated vasodilation, achieving vasodilation instead through mitochondria-derived H2O2. Mitochondrial dynamics is an important autoregulatory mechanism that contributes to mitochondrial and endothelial homeostasis and plays a role in the formation of reactive oxygen species (ROS), including H2O2. Dysregulation of mitochondrial dynamics leads to increased ROS production, decreased ATP production, impaired metabolism, activation of pathological signal transduction, impaired calcium sensing, and inflammation. We hypothesize that dysregulation of endothelial mitochondrial dynamics plays a crucial role in the endothelial microvascular dysfunction seen in individuals with CAD. Therefore, proper regulation of endothelial mitochondrial dynamics may be a suitable treatment for individuals with endothelial microvascular dysfunction, and we furthermore postulate that improving this microvascular dysfunction will directly improve outcomes for those with CAD.

Keywords: endothelial cell biology; endothelial microvasculature; microcirculation; mitochondrial dynamics.

Publication types

  • Review
  • Editorial

MeSH terms

  • Animals
  • Coronary Artery Disease / metabolism
  • Coronary Artery Disease / physiopathology
  • Endothelial Cells / metabolism
  • Endothelium, Vascular* / metabolism
  • Endothelium, Vascular* / physiopathology
  • Humans
  • Mitochondria / metabolism
  • Mitochondria, Heart / metabolism
  • Mitochondria, Heart / pathology
  • Mitochondrial Dynamics*
  • Nitric Oxide / metabolism
  • Reactive Oxygen Species / metabolism
  • Vasodilation

Substances

  • Reactive Oxygen Species
  • Nitric Oxide