小分子RNA与心血管疾病PPT.ppt

MicroRNAs in Vascular Disease ;MiroRNAs;Pathway of Genetic Information Flow and RNA “revolution” ;Discovery of miRNA - The second RNA “revolution”;miRNAs and siRNAs ;miRNAs in diseases;MiRNAs in cardiovascular disease;Animal Model Selection;Hypothesis ;MiRNAs in vascular neointimal lesion formation;Rat carotid artery balloon injury;MiRNA expression signature in normal rat carotid artery ;MiRNAs are aberrantly expressed in rat carotid arteries after angioplasty ; The time course changes of miRNAs that were highly expressed in rat carotid artery and over 1-fold upregulated after angioplasty;The time course changes of miRNAs that were highly expressed in rat carotid artery and over 50% downregulated after angioplasty;Confirmation of the aberrant miRNA expression in injured arteries by qRT-PCR and / or Northern blot analysis. ;Do these aberrantly expressed miRNAs play a role in vascular neointimal lesion formation?;miR-21 inhibitor;Local oligo delivery into the injured vascular wall;The effect of miR-21 on neointimal formation after angioplasty;What are the cellular mechanisms involved in miR-21 mediated effect on neointimal formation?;2OMe-miR-21 decreases the miR-21 expression level in cultured VSMCs in a dose-dependent manner;2OMe-miR-21 decreases VSMC proliferation in vitro;Representative BrdU stained photomicrographs (bottom panel) as well as their corresponding total cell photomicrographs (top panel);What is the effect of miR-21 on VSMC apoptosis?;The effect of miR-21 on VSMC apoptosis in vitro;Representative TUNEL stained photomicrographs (bottom panel) as well as their corresponding total cell photomicrographs (top panel);2OMe-miR-21 decreases VSMC proliferation in vivo in balloon injured vessels;2OMe-miR-21 increases VSMC apoptosis in vivo in balloon injured vessels;Potential gene targets in miR-21-mediated cellular effects on VSMCs ; computational analysis of miR-21 targets;TGF-beta is not a gene target for miR-21;Bcl-2 is not a direct target of miR-21;PTE