Cerebral cavernous malformations: from CCM genes to endothelial cell homeostasis

Trends Mol Med. 2013 May;19(5):302-8. doi: 10.1016/j.molmed.2013.02.004. Epub 2013 Mar 15.


Cerebral cavernous malformations (CCMs) are vascular lesions that can occur sporadically or as a consequence of inherited loss-of-function mutations, predominantly in the genes CCM1 (KRIT1), CCM2 (MGC4607, OSM, Malcavernin), or CCM3 (PDCD10, TFAR15). Inherited, familial CCM is characterized by the development of multiple lesions throughout a patient's life leading to recurrent cerebral hemorrhages. Recently, roles for the CCM proteins in maintaining vascular barrier functions and quiescence have been elucidated, and in this review we summarize the genetics and pathophysiology of this disease and discuss the molecular mechanisms through which CCM proteins may act within blood vessels.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Central Nervous System / metabolism
  • Central Nervous System / pathology
  • Endothelial Cells / metabolism
  • Hemangioma, Cavernous, Central Nervous System / etiology*
  • Hemangioma, Cavernous, Central Nervous System / pathology*
  • Homeostasis / genetics
  • Humans
  • KRIT1 Protein
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism


  • Apoptosis Regulatory Proteins
  • CCM2 protein, human
  • Carrier Proteins
  • KRIT1 Protein
  • KRIT1 protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • PDCD10 protein, human
  • Proto-Oncogene Proteins