Mechanisms of aortic stenosis

J Cardiol. 2018 Mar;71(3):215-220. doi: 10.1016/j.jjcc.2017.11.007. Epub 2017 Dec 16.


The pathobiology of degenerative aortic valve stenosis (AS) is complex and involves multiple features such as fibrosis, inflammation, oxidative stress, angiogenesis, hemorrhage, and osteogenic differentiation. We summarize the mechanism of valve calcification and angiogenesis which is necessary for calcifying processes. A promising therapeutic target is nuclear factor (NF)-κB which activates bone morphogenetic protein (BMP)2 via interleukin-6. BMP2 activates Wnt signaling via msh homeobox 2 causing osteogenic differentiation. BMP2 also activates Runx2/Cbfa1 which is an osteoblast-specific transcription factor. Signals in the hypoxia-inducible factor-2 axis activated by the NF-κB signaling pathway also play important role in calcifying processes including angiogenesis. The reason why angiogenesis takes place in avascular valves is still unknown, but it is likely angiogenesis and angiogenesis-related hemorrhage play critical roles in the progression of AS.

Keywords: Angiogenesis; Aortic stenosis; Intraleaflet hemorrhage; Osteogenic differentiation.

Publication types

  • Review

MeSH terms

  • Aortic Valve / physiopathology
  • Aortic Valve Stenosis / complications
  • Aortic Valve Stenosis / etiology
  • Aortic Valve Stenosis / pathology*
  • Basic Helix-Loop-Helix Transcription Factors
  • Bone Morphogenetic Protein 2 / metabolism
  • Calcinosis / etiology
  • Calcinosis / physiopathology*
  • Cell Differentiation
  • Disease Progression
  • Humans
  • NF-kappa B / metabolism
  • Neovascularization, Pathologic / etiology
  • Neovascularization, Pathologic / physiopathology*
  • Osteogenesis / physiology
  • Signal Transduction


  • BMP2 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Bone Morphogenetic Protein 2
  • NF-kappa B
  • endothelial PAS domain-containing protein 1