Abstract:
Elastic blood vessels provide capacitance and pulse-wave dampening, which are critically important in a pulsatile circulatory system. By studying newborn mice with reduced (Eln(+/)(-)) or no (Eln(-)(/)(-)) elastin, we determined the effects of altered vessel elasticity on cardiovascular development and function. Eln(-)(/)(-) mice die within 72 hours of birth but are viable throughout fetal development when dramatic cardiovascular structural and hemodynamic changes occur. Thus, newborn Eln(-)(/)(-) mice provide unique insight into how a closed circulatory system develops when the arteries cannot provide the elastic recoil required for normal heart function. Compared with wild type, the Eln(-)(/)(-) aorta has a smaller unloaded diameter and thicker wall because of smooth muscle cell overproliferation and has greatly reduced compliance. Arteries in Eln(-)(/)(-) mice are also tortuous with stenoses and dilations. Left ventricular pressure is 2-fold higher than wild type, and heart function is impaired. Newborn Eln(+/)(-) mice, in contrast, have normal heart function despite left ventricular pressures 25% higher than wild type. The major vessels have smaller unloaded diameters and longer lengths. The Eln(+/)(-) aorta has additional smooth muscle cell layers that appear in the adventitia at or just before birth. These results show that the major adaptive changes in cardiovascular hemodynamics and in vessel wall structure seen in the adult Eln(+/)(-) mouse are defined in late fetal development. Together, these results show that reduced elastin in mice leads to adaptive remodeling, whereas the complete lack of elastin leads to pathological remodeling and death.
摘要:
弹性血管提供电容和脉搏波衰减,在脉动循环系统中至关重要。通过研究具有减少(Eln(/)(-))或没有(Eln(-)(/)(-))弹性蛋白的新生小鼠,我们确定了血管弹性改变对心血管发育和功能的影响。Eln(-)(/)(-)小鼠在出生后72小时内死亡,但是当发生剧烈的心血管结构和血液动力学变化时,在整个胎儿发育过程中都可以存活。因此,新生Eln(-)(/)(-)小鼠提供了独特的见解,以了解当动脉无法提供正常心脏功能所需的弹性后坐力时,封闭的循环系统如何发展。与野生型相比,由于平滑肌细胞过度增殖,Eln(-)(/)(-)主动脉具有较小的空载直径和较厚的壁,并且大大降低了顺应性。Eln(-)(/)(-)小鼠的动脉也曲折,伴有狭窄和扩张。左心室压力比野生型高2倍,心脏功能受损。新生Eln(+/)(-)小鼠,相比之下,尽管左心室压力比野生型高25%,但心功能正常。主要血管具有较小的卸载直径和较长的长度。Eln(/)(-)主动脉在出生时或出生前在外膜中出现额外的平滑肌细胞层。这些结果表明,在成年Eln(/)(-)小鼠中观察到的心血管血液动力学和血管壁结构的主要适应性变化是在胎儿发育后期定义的。一起,这些结果表明,小鼠弹性蛋白的减少导致适应性重塑,而弹性蛋白的完全缺乏导致病理性重塑和死亡。