心肌肥厚的早期分子机制-英文课件.ppt

1、Early Molecular Mechanism Underlying Cardiac Hypertrophy,Youyi Zhang Institute of Vascular Medicine Peking University Third Hospital,12 nm,电压依赖L型钙通道,Pathological factors,Hormones,Neurotransmitters,Cytokines,Force,Function maintenance,Heart failure,Pressure-Overload Hypertrophy Model Induced by Aorti

2、c Stenosis,Hypertrophy,47 weeks,LCC-RyR Coupling During Hypertrophy,Percentage of Ca2+ sparks triggered by the first Ca2t sparklets,Percentage of depolarization pulses that occurred without triggering any Ca2+ sparks,Time constant for LCC-RyR coupling,How Is LCC-RyR Intermolecular Failure Linked to

3、the Global Performance of E-C Coupling,?,Ca2+ spikes tended to be desynchronized,Time delay from depolarization to the peak of each Ca2+ spike,*,Cellular Tolerance Against Intermolecular Failure,Numerical Simulation of Stability Margin,Seeking Potential Mechanisms Underlying the Intermolecular Failu

4、re,?,SR Ca2+ Load in Resting Cells,ALCC RyR Overlay,Con,CHT,DHT,Structural Arrangement between SR and Cell/T-tubule,0,0.02,0.04,0.06,0.08,0.10,0.12,Sham,CHT,mRNA expression (JP-2/GAPDH),*,Junctophilin2,Ca,LCC,Ryr,SR,Ca,12 nm,Potential Mechanism of Intermolecular Failure,Research Highlight,These resu

5、lts suggest that in heart failure, there is a state of intermolecular failure that proceeds without altering cellular function. So, targeting this period at a very early stage of the condition suggests perhaps by LCC inactivation or regulation of junctophilin mightbe beneficial in the prevention of heart failure.,Nature Reviews Drug Discovery 2007.4,致 谢,￥: 科技部“973”计划 国家自然科学基金委,北京大学生命科学院 王世强 课题组,北京大学第三医院 张幼怡 课题组,Experimental Support of Stability Margin,Morphology of Ventricular Muscle Cells in Cardiac Hypertrophy,Hypertrophy is the important p