The role of mitochondria in angiogenesis

  • Andrew Reichard
  • Kewal Asosingh


Angiogenesis extends pre-existing blood vessels to improve oxygen and nutrient delivery to inflamed or otherwise hypoxic tissues. Mitochondria are integral in this process, controlling cellular metabolism to regulate the proliferation, migration, and survival of endothelial cells which comprise the inner lining of blood vessels. Mitochondrial Complex III senses hypoxic conditions and generates mitochondrial reactive oxygen species which stabilize hypoxia-inducible factor (HIF-1α) protein. HIF-1α induces the transcription of the vegfa gene, allowing the translation of vascular endothelial growth factor protein, which interacts with mature and precursor endothelial cells, mobilizing them to form new blood vessels. This cascade can be inhibited at specific points by means of gene knockdown, enzyme treatment, and introduction of naturally occurring small molecules, providing insight into the relationship between mitochondria and angiogenesis. This review focuses on current knowledge of the overall role of mitochondria in controlling angiogenesis and outlines known inhibitors that have been used to elucidate this pathway which may be useful in future research to control angiogenesis in vivo.


Angiogenesis Mitochondria Endothelial mROS HIF-1α VEGF 



The authors thank Dave Schumick of The Cleveland Clinic Center for Medical Art and Photography for his illustration work on Fig. 1. Grant support provided by National Institutes of Health Grants HL103453, HL081064, HL109250, HL60917, and HL115008, the Alfred Lerner Memorial Chair in Innovative Biomedical Research at the Cleveland Clinic, and in part by the Lerner Research Institute Center of Excellence in Pulmonary Vascular Disease.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Department of Inflammation and Immunity, Lerner Research InstituteThe Cleveland ClinicClevelandUSA
  2. 2.Flow Cytometry Core, Lerner Research InstituteThe Cleveland ClinicClevelandUSA

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