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.

Keywords: VEGF-A(165)–isoforms–intracranial atherosclerosis–moyamoya disease.