Expression of hypoxia-inducible angiogenic proteins (hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and E26 transformation-specific-1) and plaque hemorrhage in human carotid atherosclerosis.

Abstract

OBJECT:

Plaque hemorrhage in carotid atherosclerosis promotes plaque progression, resulting in cerebrovascular disease. Hypoxia inducible factor-1alpha (HIF-1alpha) induces angiogenesis via the expression of vascular endothelial growth factor (VEGF) and E26 transformation-specific-1 (Ets-1). The authors investigated human carotid plaques to determine whether these hypoxia-inducible angiogenic proteins play a major role in intraplaque angiogenesis and hemorrhage.

METHODS:

The expression of HIF-1alpha, VEGF, and Ets-1 was analyzed using immunohistochemistry and Western blotting in 29 human carotid plaques obtained at carotid endarterectomy. The authors investigated the relationship between plaque characteristics and clinical symptoms.

RESULTS:

A higher incidence of plaque hemorrhage was observed in plaques associated with symptoms than in those without symptoms (p = 0.03). Hypoxia-inducible factor-1alpha, VEGF, and Ets-1 coexisted in the deep layer of plaque, where angiogenesis was remarkably developed; the expression levels of HIF-1alpha, VEGF, and Ets-1 were significantly enhanced in the main lesion of the plaque (p < 0.01). Symptomatic plaques showed higher expression of VEGF (p = 0.04) than asymptomatic plaques. Plaques with hemorrhage showed a higher incidence of plaque ulcer (p = 0.001) and higher expression of Ets-1 (p = 0.03) than those without hemorrhage. Moreover, significantly increased expressions of VEGF (p = 0.01) and Ets-1 (p = 0.006) were observed in plaques with not only hemorrhages but also ulcers and severe stenosis.

CONCLUSIONS:

The findings in this study suggest that hypoxia-inducible angiogenic proteins in human carotid atherosclerosis promote intraplaque angiogenesis, which can induce plaque hemorrhage and progression.

• Authors: Tetsuhiro Higashida, Hiroshi Kanno, Masato Nakano, Kengo Funakoshi, Isao Yamamoto
• Journal: Journal of neurosurgery (J Neurosurg) Vol. 109 Issue 1 Pg. 83-91 (Jul 2008) ISSN: 0022-3085 [Print] United States
• PMID: 18590436 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ETS1 protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Proto-Oncogene Protein c-ets-1
• Vascular Endothelial Growth Factor A

Topics

• Aged
• Atherosclerosis (complications, metabolism, pathology)
• Carotid Artery Diseases (complications, metabolism, pathology)
• Case-Control Studies
• Cohort Studies
• Female
• Hemorrhage (etiology, metabolism, pathology)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Male
• Middle Aged
• Neovascularization, Pathologic (complications, metabolism, pathology)
• Proto-Oncogene Protein c-ets-1 (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)