Endothelial cells from human cerebral aneurysm and arteriovenous malformation release ET-1 in response to vessel rupture

Int J Mol Med. 2006 Nov;18(5):813-9.


Cerebral aneurysms and arteriovenous malformations (AVM) are a common cause of stroke and cerebral hemorrage. Both are often discovered when they rupture, causing subarachnoid hemorrhage (SAH). SAH-induced vasospasm is mediated by enhanced vasoconstriction due to endothelin-1 (ET-1). We investigated whether endothelial cells (ECs) obtained from aneurysm and AVM express phenotypic and genotypic alterations contributing to the development of vasospasm after SAH. We isolated ECs from human AVM and aneurysm and then confirmed their EC origin by polymerase chain reaction and immunocytochemistry with endothelial markers. Experiments were also carried out with human cerebral microvascular and umbilical vein ECs (HCECs and HUVECs respectively) for comparison. We tested EC proliferation ability and microtubule formation in Matrigel at different cell passages. Five aneurysm (3 ruptured, 2 unruptured) and 3 AVM (2 ruptured, 1 unruptured) ECs were tested for ET-1 release in the culture medium. Aneurysm and AVM ECs expressed von Willebrand factor, Adrenomedullin, and exhibited a progressive reduction of proliferation and in vitro angiogenic ability after the V passage. Significantly higher levels of ET-1 have been detected in ECs from ruptured aneurysms and AVMs. We report the first successful isolation and characterization of primary EC lines from human cerebral vascular lesions. Augmented release of ET-1 is correlated with the rupture of the abnormal vessel confirming its role in vasospasm after SAH. Furthermore, ECs obtained from these vascular malformations can be used as an experimental model to study SAH-induced vasoconstriction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenomedullin / genetics
  • Adrenomedullin / metabolism
  • Cell Line
  • Constriction, Pathologic
  • Endothelial Cells / chemistry
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Endothelin-1 / analysis
  • Endothelin-1 / genetics
  • Endothelin-1 / metabolism*
  • Endothelium, Vascular / chemistry
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology
  • Humans
  • Intracranial Aneurysm / metabolism*
  • Intracranial Aneurysm / pathology
  • Intracranial Arteriovenous Malformations / metabolism*
  • Intracranial Arteriovenous Malformations / pathology
  • Protein Transport
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Rupture, Spontaneous / metabolism
  • Rupture, Spontaneous / pathology
  • Subarachnoid Hemorrhage / metabolism*
  • Subarachnoid Hemorrhage / pathology
  • von Willebrand Factor / genetics
  • von Willebrand Factor / metabolism


  • Endothelin-1
  • RNA, Messenger
  • von Willebrand Factor
  • Adrenomedullin