Differential Expression of Vascular Endothelial Growth Factor-A165 Isoforms Between Intracranial Atherosclerosis and Moyamoya Disease.

Abstract

BACKGROUND:

Vascular endothelial growth factor-A165 (VEGF-A165) has been identified as a combination of 2 alternative splice variants: proangiogenic VEGF-A165a and antiangiogenic VEGF-A165b. Intracranial atherosclerotic disease (ICAD) and moyamoya disease (MMD) are 2 main types of intracranial arterial steno-occlusive disorders with distinct capacities for collateral formation. Recent studies indicate that VEGF-A165 regulates collateral growth in ischemia. Therefore, we investigated if there is a distinctive composition of VEGF-A165 isoforms in ICAD and MMD.

METHODS:

Sixty-six ICAD patients, 6 MMD patients, and 5 controls were enrolled in this prospective study. ICAD and MMD patients received intensive medical management upon enrollment. Surgery was offered to 9 ICAD patients who had recurrent ischemic events, 6 MMD patients, and 5 surgical controls without ICAD. VEGF-A165a and VEGF-A165b plasma levels were measured at baseline, within 1 week after patients having surgery, and at 1, 3, and 6 months after treatment.

RESULTS:

A significantly higher baseline VEGF-A165a/b ratio was observed in MMD compared to ICAD (P = .016). The VEGF-A165a/b ratio increased significantly and rapidly after surgical treatment in ICAD (P = .026) more so than in MMD and surgical controls. In patients with ICAD receiving intensive medical management, there was also an elevation of the VEGF-A165a/b ratio, but at a slower rate, reaching the peak at 3 months after initiation of treatment (baseline versus 3 months VEGF-A165a/b ratio, P = .028).

CONCLUSIONS:

Our study shows an increased VEGF-A165a/b ratio in MMD compared to ICAD, and suggests that both intensive medical management and surgical revascularization elevate the VEGF-A165a/b ratio in ICAD patients.

• Authors: Hao Jiang, Juan F Toscano, Michael Schiraldi, Shlee S Song, Konrad H Schlick, Oana M Dumitrascu, Raymond Liou, Patrick D Lyden, Jianwei Pan, Renya Zhan, Jeffrey L Saver, Nestor R Gonzalez
• Journal: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association (J Stroke Cerebrovasc Dis) Vol. 28 Issue 2 Pg. 360-368 (Feb 2019) ISSN: 1532-8511 [Electronic] United States
• PMID: 30392834 (Publication Type: Comparative Study, Journal Article, Multicenter Study)
• Copyright: Copyright © 2018. Published by Elsevier Inc.

Chemical References

• Biomarkers
• Protein Isoforms
• VEGFA protein, human
• Vascular Endothelial Growth Factor A

Topics

• Adult
• Biomarkers (blood)
• Case-Control Studies
• Female
• Humans
• Intracranial Arteriosclerosis (blood, diagnosis, therapy)
• Los Angeles
• Male
• Middle Aged
• Moyamoya Disease (blood, diagnosis, therapy)
• Prospective Studies
• Protein Isoforms
• Time Factors
• Treatment Outcome
• Vascular Endothelial Growth Factor A (blood)