G Protein Coupled Singnal Transduction In The Pathogenesis Of Vasovagal Syncope

Vasovagal syncope(VVS)is transient loss of consciousness triggered by a variety of factors,due to a sudden drop of blood pressure(BP)caused by reflex peripheral vasodilatation and reduced cerebral blood flow.The nature of VVS is a reflex syncope,which is attributed to the dysfunction of blood pressure,heart rate regulation and autonomic nervous system.G protein-coupled signal transduction pathways represent the molecular mechanisms of cardiovascular reflexes.Heterotrimeric guanine nucleotide-binding proteins(G proteins)are responsible for the signal transduction from the cell surface,which have great importance in the regulation of arterial pressure or its disturbances.We study the role of G protein-coupled signal transduction and their contribution to the mechanism of vasovagal syncope,which may help to discover novel biomarkers of VVS and new strategies of therapy.Syncope can be induced by a head-up tilt test(HUT),a major diagnostic tool for evaluating patients with vasovagal syncope.This study consists of two parts.The first part we undertook to study the expression profile of peripheral lymphocytes from vasovagal syncope cases and their age and gender matched normal controls employing an expression microchip approach.Perform cluster analysis and select the differentially genes by software such as bioinformatics Affy Expression and Stanford TM4(the SAM,LIMMA).The selected differentially expressed genes were annotated using DAVID(GO).In this study,there are total 103 differentially expressed genes,among which 100 genes were up-regulated,with the another three were down-regulated.Two genes,GNG2 and GPR174,were confirmed in accordance with the G protein-coupled signal transduction,also validated the result of microarray method by quantitative PCR.Through signaling pathway study on differentially expressed genes by David(KEGG)database,this study gets a total nine signaling pathways,including apoptosis,chemokine,etc.The second part,we study the association with the polymorphism of the genes RGS2C1114 G,ADRB1ser49gly and GNB3C825 T which related with G protein-coupled signal transduction and vasovagal syncope by using high-resolution melting curve HRM combined with gene sequencing method.A total of 232 cases of Han unexplained syncope children and 100 normal controls enrolled,the results showed there is no obvious correlation between gene polymorphism and vasovagal syncope.There is a different expression profiling of vasovagal syncope with the normal control by employing an expression microchip approach.Two genes,GNG2 and GPR174,among vasovagal syncope group were up-regulated,indicating that G protein-coupled signal transduction involved in vasovagal syncope.While among the population in this study,there is no evidence to show any association with the polymorphism of the genes ADRB1ser49 gly GNB3C825T and RGS2C1114 G,which related with G protein signal transduction and vasovagal syncope.