Differential Expression Of RBM3 And VEGF In Cerebral Arteriovenous Malformation Study And Related Mechanisms

Cerebral arteriovenous malformation(c AVM) is one of the common neurosurgical cerebrovascular disease,and one of factors that make teenagers disability and death.Cerebral arteriovenous malformations(AVMs) are abnormal vascular connections that form between arteries and veins, without an intervening capillary bed or neuronal tissues[1].They are a heterogeneous group of vascular lesions varying in locations,sizes,and venous drainages. More common in the frontal lobe,temporal lobe,parietal lobe,other parts such as occipital lobe,cerebellum,brainstem also occurred.The incidence of cerebral AVMs in the general population is less than 1%.AVMs may be clinically silent or present with reiterative hemorrhages,seizures, headaches, dizziness and so on.The pathogenesis of AVMs remains incompletely elucidated and has traditionally been thought to be congenital.The embryonic development of the original cerebrovascular begin to differentiate into arteries, veins and capillary network during the third week.At this point the arteries and veins parallel arrangement, adjacency closely.If the vessel is retarded, arteriovenous will be formed between communication, will be the formation of arteriovenous malformation.A Previous studies found that the brain arteriovenous malformation of artery part already mature, and part of venous blood vessels also stays in the embryonic period, considered deformity caused by venous developmental disorders.Studies of surgically-resected AVM tissue suggest an active angiogenic and inflammatory lesion rather than a static congenital anomaly. Several groups [2,3] have shown that a prominent feature of the AVM phenotype is relative overexpression of vascular endothelial growth factor(VEGF-A), at both the m RNA and protein level. Extrapolating from animal models,VEGF may contribute to the hemorrhagic tendency of AVMs. Endothelial cells derived from AVMs expressed high levels of vascular endothelial growth factor A and significantly overexpressed the vascular endothelial growth factor receptors 1and 2, as compared with control endothelial cells.RNA binding motif protein 3(RBM3) belonging to one of the highly conserved RNA-binding protein family,is an important kind of cold shock protein exists in mammalian cells,its expression quantity increases in low temperature, ischemia, hypoxia environmenta[4].RBM3 enhances COX-2, IL-8 and VEGF m RNA stability and translation[5].cerebral arteriovenous malformation arteriolar long-term is in a state of high flow, high pressure, the secondary deformities of "steal blood" phenomenon, cause the surrounding brain tissue ischemia, hypoxia, stimulate secretion related factors, so we speculated that it was due to the interaction between these factors and related factors, promote angiogenesis of arteriovenous malformation and reshaping.Objective:Through testing the expression of RNA-binding motif protein 3(RBM3) and vascular endothelial growth factor(VEGF) in the arteriovenous malformation malformation.Combined with the clinical and imaging features,to explore the correlation of the expression of RBM3 and VEGF between the state of hemodynamics in c AVM.We will provide a new clue to study on molecular biology of venous malformation,and clarify the association between RBM3, VEGF and its developmental regulation of vascular function.Method:35 cases with arteriovenous malformation, and 6 cases′s brain tissue with epilepsy that has been diagnosed by digital subtraction angiography(DSA), MRI and pathologica,underwent surgery in department of surgery of Beijing Tiantan Hospital. With the help of digital subtraction angiography(DSA),patients with cerebral venous malformation into two groups, according to the partition interval(A-V),which comes from the blood through artery to vein,that express the state of hemodynamics.The two groups are: high flow(A-V≤2 frame)(Fig.1), 19 cases and low flow(A-V>2 frame)(Fig.2), 16 cases.To obtain each paraffin embedded specimens comes from the patients with brain arteriovenous malformation and operate them by immunohistochemical technique and detect the expression of RBM3 and VEGF,then analysis the correlation of the expression level of RBM3,VEGF ligand and the state of hemodynamics by the SPSS 19.0.Results:(1)RBM3 in low-flow arteriovenous malformation group( 52.6%) and a high-flow group( 93%) of positive expression are higher than in normal brain endothelial cells positive rate, the difference was significant in the statistically(P<0.01)(Table 1);The expression of RBM3 in arteriovenous malformations of low flow group and high flow group has a statistically significant differences(P < 0.01)(Table 2).The correlation analysis results by SPSS 19.0 is P<0.01, considered that the expression level of RBM3 and the state of hemodynamic have relevance, the correlation coefficient is C=0.672.(2)The expression of RBM3 in arteriovenous malformations of hemorrhage group and nonhemorrhage group has no statistically significant differences(P > 0.05)(Table 3).(3)The different of VEGF in low-flow arteriovenous malformation group and a high-flow group of positive expression has no statistically significant differences(P>0.05)(Table 4);The expression of VEGF in arteriovenous malformations of hemorrhage group and nonhemorrhage group has no statistically significant differences(P>0.05)(Table 5).(4)The relevance of RBM3 and VEGF in cerebral arteriovenous malformations Tissues:the expression of the protein of RBM3 and VEGF have no correlation in cerebral arteriovenous malformation tissue(P>0.05)(Table 6).Conclusion:(1)RBM3 don’t express or low expression in the vasscullar of normal brain tissue,but is highly expressed in the arteriovenous malformation and with the blood flow its expression level is increasing.The results suggest that RBM3 and arteriovenous malformations associated,and its expression were affected by hemodynamic vascular malformation.The expression of RBM3 in arteriovenous malformations of hemorrhage group and nonhemorrhage group has no statistically significant differences,the expression of RBM3 has nothing to do with hemorrhage.(2)The expression of VEGF in arteriovenous malformations of hemorrhage group and nonhemorrhage group has no statistically significant differences, the expression of VEGF has nothing to do with hemorrhage.(3)RBM3 and VEGF expressed in arteriovenous malformation rises but no correlation between them, may be in the influence of cerebral arteriovenous malformation generated in the process of the affected by different factors may also be associated with the individual differences of specimen.It is suggested that both may be stimulated by different predisposing factors and signal transduction pathways.