Increased angiogenesis and angiogenic gene expression in carotid artery plaques from symptomatic stroke patients

Neurosurgery. 2006 May;58(5):971-7; discussion 971-7. doi: 10.1227/01.NEU.0000210246.61817.FE.


Objective: Carotid plaque rupture is one of the main causes of stroke by creating cerebral emboli. The biochemical, molecular, and structural factors that promote carotid plaque rupture are not yet understood in detail. We hypothesize that increased microvascular blood flow within a carotid plaque might fissure the plaque, elevate local pressure, and promote plaque rupture. The aim of this study is to determine the role of angiogenesis and angiogenesis-related gene expression in symptomatic carotid plaque.

Methods: The present study evaluated the new vessel formation (using hematoxylin-eosin staining and CD34 immunohistochemistry) and angiogenic gene expression (using microarray and real-time polymerase chain reaction analysis) in carotid plaque specimens obtained during endarterectomy from 13 symptomatic stroke patients in comparison with eight asymptomatic patients.

Results: Symptomatic plaques showed significantly higher new vessel density in the fibrous cap (by 347%, P < 0.05) as well as in the plaque proper (by 196%, P < 0.05) compared with the asymptomatic plaques. The fibrous caps of the plaques were threefold thinner in the symptomatic patients when compared with the asymptomatic patients. In symptomatic plaque, gene expression analysis showed increased abundance of 31 transcripts known to promote angiogenesis and cell division compared with plaques of asymptomatic patients.

Conclusion: This study suggests that angiogenic gene expression and the ensuing angiogenesis in the plaques might contribute to their destabilization and resulting symptoms.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Carotid Stenosis / genetics
  • Carotid Stenosis / metabolism*
  • Carotid Stenosis / pathology
  • Endarterectomy, Carotid / methods
  • Female
  • Gene Expression Regulation / physiology*
  • Humans
  • Male
  • Middle Aged
  • Neovascularization, Physiologic / physiology*
  • Stroke / genetics
  • Stroke / metabolism*
  • Stroke / pathology