Shear stress,the tangential component of the hemodynamic forces acting on the vascular wall,has been shown to play crucial roles in the regulation of vascular endothelial function,as well as the formation and progress...
详细信息
Shear stress,the tangential component of the hemodynamic forces acting on the vascular wall,has been shown to play crucial roles in the regulation of vascular endothelial function,as well as the formation and progression of *** studies by us,our collaborators,and others have elucidated that atheroprone shear stress modulates dysfunction of vascular endothelial cells(ECs),including aberrant proliferation,inflammation,migration,increased permeability,and releasing of some pro-atherogenic molecules,by the mediation of several molecules and factors,*** RNAs and histone deacetylases(HDACs),which are epigenetic mediators regulating gene expression without altering the underlying DNA *** of the most important molecules that have been found in our recent study is another epigenetic mediator,DNA methyltransferase 1(DNMT1),whose expression and activation could be induced by the atheroprone oscillatory shear stress(OS)but not the atheroprotective pulsatile shear stress in ECs and its inhibition attenuated OS-induced DNA hypermethylaion,proliferation,and inflammatory responses of *** the activation of upstream mechanotransduction,signaling and regulatory pathways,***,m TOR,and TLRs,OS-induced DNMT1 methylates DNA both globally and at specific loci,resulting in the changes of gene expressions(PCNA,cyclin A,KLF4,and etc.)and functional *** vivo experiments also showed increases of DNMT1 expression and DNA methylation in the partially-ligated rat carotid arteries where the shear flow is *** concluded that DNMT1 governs the effects of OS on endothelial dysfunction and atheroma *** results from the present study help to identify the hitherto poorly understood connection between DNA methylation and atheroprone hemodynamic forces applied to the vascular endothelium and to discover new target biomarkers highly associated with the translational and clinical medicine research with great potentials for b
暂无评论