YKL-40 can promote angiogenesis in sporadic cerebral cavernous malformation (CCM)

The factors affecting the formation of sporadic CCMs remain unclear. A cDNA microarray was used to identify characteristic gene expression patterns in sporadic CCMs. Transcription level of YKL-40 was confirmed by reverse transcription-polymerase chain reaction (RT-PCR). The location and expression were revealed by immunochemistry, immunofluorescence staining and level of YKL-40 was quantified by Western blotting. Alterations to endothelial function following the up or down regulation of gene expression was assessed by Transwell assays, cell counting kit-8 assays and capillary-like tube formation assays in human brain microvascular endothelial cells (HBMECs) in vitro. We generated a murine model by stereotaxically injecting HBMECs with expressing amounts of YKL-40 into the brain. cDNA microarray and RT-PCR results revealed that the transcription level of YKL-40 was ≥140-fold higher in sporadic CCMs in healthy controls. Histological staining revealed excessive YKL-40 expression in the CCM endothelium. Western blotting results analysis showed that YKL-40 protein expression was significantly higher in CCM endothelium (P < 0.05). YKL-40 over-expressing HBMECs showed increased cell proliferation, migration and tube formation ability compared with the control group, whereas downregulating of YKL-40 inhibited the proliferation, migration of HBMECs and capillary-like tube formation (P < 0.05). In animals, increased of YKL-40 was associated with abnormal vascular lesions that were similar to CCMs. YKL-40 is over-expressed in the CCM endothelium and acts as an angiogenic factor that promotes the pathogenesis of sporadic CCMs. YKL-40 may therefore represent a potential therapeutic target in the treatment of sporadic CCM.