生物机械力启动血管重塑和平滑肌细胞信号传导.pptVIP

CONCLUSION Biomechanical stresses can initiate multi-intracellular signal pathways like growth factors, vas-active peptides leading to cardiovascular remodeling Arteriosclerotic factors (e.g., ApoE-/-, and p53-/-) can accelerate mechanical stresses-induced cardiovascular remodeling * Yanhua Hu Gertraud Sturm Ursula Huemer Gottfried Baier Qingbo Xu Manuel Mayr Anya Jenewen Thomas Ottl ACKNOWLEGMENTS Georg Wick Institute of Biomedical Aging Research, Austrian Academy of Sciences, Austria * * * * * * * * * * * * * Biomechanical Stress-initiated Vascular Remodeling and Signal Transduction in Smooth Muscle Cells Department of Histology Embryology School of Basic Medical Sciences Zhongshan University GUANGZHOU, P.R.CHINA Chaohong Li 李 朝 红 中山大学基础医学院组胚教研室 Page 85 * Sympathetic nervous system Vascular remodeling (arteriosclerosis) Heart remodeling (heart failure) Main Causes to Mortality and Morbidity Hypertension Biomechanical stresses Renin-angiotensin system HYPOTHESIS-DRIVEN WORKING MODEL * Biomechanical Stress Stretch stress: created by blood pressure Shear stress: created by fluid flow across Shear stress (EC) Stretch stress (EC,SMC, F) Blood flow INTRODUCTION * Normal mechanical stress is essential for normal development, differentiation, and phenotype maintenance. Hypertension-initiated abnormal mechanical stress induces vascular remodeling INTRODUCTION * 1. How do the cells sense and transduce the extracellular mechanical stimuli into intracellular biochemical signals leading to cardiovascular remodeling? Questions ? 2. Are there mechanoreceptors in cell membranes? HYPOTHESIS-DRIVEN WORKING MODEL * Animal models of gene manipulating (Gene knockout) PKCdelta-/-, G protein gamma 11-/-, p53-/-, ApoE-/- mice Mechanical stress models (in vivo and in vitro) Functional consequences EXPERIMENTAL DESIGN * Molecular mechanisms of biomechanical stress-initiated remodeling of Vessels Heart * Vessels in vitro: Signa