The association between high VEGF levels and multiple probable punctuate cavernous malformations

Abstract

Cerebral cavernous malformations (CCMs) are congenital abnormalities of the cerebral vessels. The de novo development of new lesions in this disease has been reported. However, the underlying mechanism of progressive CCMs in such patients remains unclear. This report documents two cases of multiple probable CCMs that showed a progressive behaviour. The plasma levels of vascular endothelial growth factor (VEGF), and transforming growth factor-beta1 (TGF-beta1) were measured using an enzyme-linked immunosorbent assay (ELISA). The concentration of both VEGF and TGF-beta1 in plasma was increased in these patients. A relationship was observed between high concentrations of growth factors and progressive CCMs. Even though a causal linkage between these conditions cannot be confirmed, a continuous high VEGF level in plasma could be a possible clinical indicator for subsequent intracerebral haemorrhages in the CCM patients.

KRIT1 Protein Depletion Modifies Endothelial Cell Behavior via Increased Vascular Endothelial Growth Factor (VEGF) Signaling

“…However, VEGF is a known regulator of pathological angiogenesis (63); thus the suggestion that VEGF/ KRIT1 cross-talk could have a function in the formation of CCM is an obvious one. Intermittent reports of increased VEGF expression in lesions or serum of CCM patients (64,65) correlate nicely with our discovery that Krit1 ϩ/Ϫ mice have higher serum levels of VEGF-A (15). However, interpretation of these clinical reports is limited by small group size and the inclusion of both sporadic and hereditary CCMs; therefore, the clinical import of VEGF signaling remains unclear.…”

Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin

“…Nonetheless, increased expression of several pro-angiogenic growth factors have been found in human CCM lesions, including VEGF, PDGF, and TGF-β (Abe et al, 2009, Jung et al, 2003, Maiuri et al, 2006, Yildirim et al, 2010), and increased VEGF expression has also been measured in KRIT1 deficient animals (Corr et al, 2012). DiStefano et al showed that loss of KRIT1 increases VEGF expression by increasing nuclear β-catenin (DiStefano et al, 2014), where β-catenin stimulates transcription of VEGF (Glading and Ginsberg, 2010).…”

Chronic Encapsulated Intracerebral Hematoma Associated with Cavernous Malformation

“…It is known that CM may be induced by radiation therapy or radiosurgery11,20), whereas de novo formations of CM without previous radiotherapy are rare1,2,3,5,8). Recent studies have demonstrated that the endothelial proliferation induced by VEGF may also contribute to de novo formation of CM1,5). It is possible that CM developed de novo in the present case, however, we could not definitively confirm that hypothesis because the previous MRI had been performed on a 1.5 tesla device.…”