Pezet Mylène, Jacob Marie-Paule, Escoubet Brigitte, Gheduzzi Dealba, Tillet Emmanuelle, Perret Pascale, Huber Philippe, Quaglino Daniela, Vranckx Roger, Li Dean Y, Starcher Barry, Boyle Walter A, Mecham Robert P, Faury Gilles
Université Joseph Fourier, UFR de Biologie, Grenoble, France.
Rejuvenation Res. 2008 Feb;11(1):97-112. doi: 10.1089/rej.2007.0587.
Elastin, the main component of elastic fibers, is synthesized only in early life and provides the blood vessels with their elastic properties. With aging, elastin is progressively degraded, leading to arterial enlargement, stiffening, and dysfunction. Also, elastin is a key regulator of vascular smooth muscle cell proliferation and migration during development since heterozygous mutations in its gene (Eln) are responsible for a severe obstructive vascular disease, supravalvular aortic stenosis, isolated or associated to Williams syndrome. Here, we have studied whether early elastin synthesis could also influence the aging processes, by comparing the structure and function of ascending aorta from 6- and 24-month-old Eln+/- and Eln+/+ mice. Eln+/- animals have high blood pressure and arteries with smaller diameters and more rigid walls containing additional although thinner elastic lamellas. Nevertheless, longevity of these animals is unaffected. In young adult Eln+/- mice, some features resemble vascular aging of wild-type animals: cardiac hypertrophy, loss of elasticity of the arterial wall through enhanced fragmentation of the elastic fibers, and extracellular matrix accumulation in the aortic wall, in particular in the intima. In Eln+/- animals, we also observed an age-dependent alteration of endothelial vasorelaxant function. On the contrary, Eln+/- mice were protected from several classical consequences of aging visible in aged Eln+/+ mice, such as arterial wall thickening and alteration of alpha(1)-adrenoceptor-mediated vasoconstriction. Our results suggest that early elastin expression and organization modify arterial aging through their impact on both vascular cell physiology and structure and mechanics of blood vessels.
弹性蛋白是弹性纤维的主要成分，仅在生命早期合成，并赋予血管弹性。随着年龄增长，弹性蛋白逐渐降解，导致动脉扩张、硬化和功能障碍。此外，弹性蛋白是发育过程中血管平滑肌细胞增殖和迁移的关键调节因子，因为其基因（Eln）的杂合突变会导致一种严重的阻塞性血管疾病——主动脉瓣上狭窄，可单独出现或与威廉姆斯综合征相关。在此，我们通过比较6个月和24个月大的Eln+/-和Eln+/+小鼠升主动脉的结构和功能，研究了早期弹性蛋白合成是否也会影响衰老过程。Eln+/-动物血压高，动脉直径较小，血管壁更硬，含有额外但更薄的弹性层。然而，这些动物的寿命未受影响。在年轻成年的Eln+/-小鼠中，一些特征类似于野生型动物的血管衰老：心脏肥大、弹性纤维碎片化增强导致动脉壁弹性丧失以及主动脉壁尤其是内膜中细胞外基质积聚。在Eln+/-动物中，我们还观察到内皮血管舒张功能的年龄依赖性改变。相反，Eln+/-小鼠免受了老年Eln+/+小鼠中可见的几种典型衰老后果的影响，如动脉壁增厚和α(1)-肾上腺素能受体介导的血管收缩改变。我们的结果表明，早期弹性蛋白的表达和组织通过对血管细胞生理学以及血管结构和力学的影响来改变动脉衰老。
