Elucidating the crosstalk between endothelial-to-mesenchymal transition (EndoMT) and endothelial autophagy in the pathogenesis of atherosclerosis

Vascul Pharmacol. 2024 Jun:155:107368. doi: 10.1016/j.vph.2024.107368. Epub 2024 Mar 26.

Abstract

Atherosclerosis, a chronic systemic inflammatory condition, is implicated in most cardiovascular ischemic events. The pathophysiology of atherosclerosis involves various cell types and associated processes, including endothelial cell activation, monocyte recruitment, smooth muscle cell migration, involvement of macrophages and foam cells, and instability of the extracellular matrix. The process of endothelial-to-mesenchymal transition (EndoMT) has recently emerged as a pivotal process in mediating vascular inflammation associated with atherosclerosis. This transition occurs gradually, with a significant portion of endothelial cells adopting an intermediate state, characterized by a partial loss of endothelial-specific gene expression and the acquisition of "mesenchymal" traits. Consequently, this shift disrupts endothelial cell junctions, increases vascular permeability, and exacerbates inflammation, creating a self-perpetuating cycle that drives atherosclerotic progression. While endothelial cell dysfunction initiates the development of atherosclerosis, autophagy, a cellular catabolic process designed to safeguard cells by recycling intracellular molecules, is believed to exert a significant role in plaque development. Identifying the pathological mechanisms and molecular mediators of EndoMT underpinning endothelial autophagy, may be of clinical relevance. Here, we offer new insights into the underlying biology of atherosclerosis and present potential molecular mechanisms of atherosclerotic resistance and highlight potential therapeutic targets.

Keywords: Atherosclerosis; Autophagy; EndoMT.

Publication types

  • Review

MeSH terms

  • Animals
  • Atherosclerosis* / genetics
  • Atherosclerosis* / metabolism
  • Atherosclerosis* / pathology
  • Atherosclerosis* / physiopathology
  • Autophagy*
  • Endothelial Cells* / metabolism
  • Endothelial Cells* / pathology
  • Epithelial-Mesenchymal Transition
  • Humans
  • Phenotype
  • Plaque, Atherosclerotic
  • Signal Transduction*