The many kinds of cell structures involved in cell-cell communication include tight junction,adherens junction and gap junction,but almost all are between adjacent cells.Recently,a general and dynamic membrane tether,termed tunneling nanotubes or membrane nanotubes(MNTs),was discovered to be involved in communication between distant cells.By facilitating intercellular communication,MNTs contribute to many biological functions and pathologic changes in cells.Many works have revealed the structure,formation and functional properties of MNTs.However,as novel structures,further research is needed.
Heart disease is associated with increased sympathetic nerve activity and elevated levels of circulating catecholamines,resulting in chronic stimulation of the β-adrenergic receptors (β-AR) and consequent pathological cardiac remodeling.Experimentally,chronic administration of the β-AR agonist isoproterenol (ISO) has been most commonly used to model β-AR-induced cardiac remodeling.However,it remains unclear whether β-AR-mediated cardiac remodeling and dysfunction differs between sustained versus pulsatile (intermittent) exposure to a β-agonist.Here,we compare the effects of intermittent versus sustained administration of ISO on cardiac remodeling and function in mice.Animals were administered 5 mg (kg d)-1 ISO for 2 weeks either by daily subcutaneous injection,or continuous infusion via an implanted osmotic minipump.Cardiac function and remodeling were determined by echocardiography,micromanometry and histology.Moreover,Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were utilized to define the proteins and genes involved.Both sustained and intermittent administration of ISO resulted in a similar degree of cardiac hypertrophy (16% and 19%,respectively).However,mice receiving ISO by daily injection developed more severe ventricular systolic and diastolic dysfunction and myocardial fibrosis compared with mice receiving ISO via the osmotic minipump.The disparity in results between the delivery methods is suggested to be due,at least in part,to increased expression of fibrogenic factors,including connective tissue growth factor (CTGF) and NADPH oxidase (NOX4),in mice receiving intermittent application of ISO.In summary,compared with sustained exposure to a β-AR agonist,intermittent β-AR stimulation leads to more severe cardiac dysfunction and fibrosis.These findings not only further our understanding of β-AR function in the setting of cardiac pathophysiology,but also highlight that significant differences can result dependent upon the mode of experimental β-AR stimulation in
MA XiaoWei1,3,SONG Yao1,3,CHEN Chao1,3,FU YongNan1,3,SHEN Qiang2,3,LI ZiJian1,3 & ZHANG YouYi1,3 1Institute of Vascular Medicine,Peking University Third Hospital,Beijing 100191,China
目的:探讨压力负荷诱导大鼠心肌肥厚和左室舒张功能的评价方法。方法:采用横向主动脉缩窄法(TAC)建立压力负荷诱导大鼠心肌重塑模型,应用超声心动图、有创血流动力学检测及心肌组织中羟脯氨酸含量测定等方法评价左室结构和舒张功能。结果:(1)超声心动图测定的TAC组术后3周大鼠左室壁厚度显著大于假手术组[前壁:(1.71±0.11)mm vs(1.43±0.06)mm,P<0.01;后壁(1.78±0.03)mm vs(1.44±0.02)mm,P<0.01];TAC组术后3周左室后壁心肌舒张早期运动速度(E')与假手术组相比显著下降[(52.1±0.8)mm.s-1vs(63.8±1.5)mm.s-1,P<0.01],术后6周进一步降低。(2)解剖称重左室重量/胫骨长度在TAC组显著高于假手术组[3周:(19.6±1.1)mg.mm-1 vs(14.8±0.6)mg.mm-1,P<0.01;6周:(23.2±0.9)mg.mm-1 vs(15.6±0.7)mg.mm-1,P<0.01]。(3)TAC组校正的左室内压力最大下降速度(dp/dtmin/LVSP)在术后3周有下降趋势(48.9±5.9 vs 63.5±9.9),术后6周下降显著(35.4±4.0 vs 54.4±2.9,P<0.01)。(4)天狼猩红染色可见TAC组血管周围胶原沉积明显多于假手术组,术后6周TAC组心肌组织中羟脯氨酸含量显著高于假手术组[(465.3±17.3)μg vs(351.4±8.2)μg,P<0.05]。结论:超声心动图组织多普勒测定左室后壁心肌运动速度是评价压力负荷心肌重塑大鼠早期左室舒张功能异常的可靠指标。
