Deletion of matrix metalloproteinase-12 compromises mechanical homeostasis and leads to an aged aortic phenotype in young mice.
Deletion of matrix metalloproteinase-12 compromises mechanical homeostasis and leads to an aged aortic phenotype in young mice.
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DOI：
10.1016/j.jbiomech.2022.111179
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发表时间：
2022-08
影响因子：
2.4
通讯作者：
Humphrey, Jay D.
中科院分区：
文献类型：
--
作者：
Spronck, Bart;Ramachandra, Abhay B.;Moriyama, Lauren;Toczek, Jakub;Han, Jinah;Sadeghi, Mehran M.;Humphrey, Jay D.
在动脉壁的正常发育之后出现机械稳态，并且此后需要细胞外基质成分在不变的机械状态内缓慢平衡降解和沉积。最近的研究结果表明，动脉老化中的稳态受到损害，这有助于老年中央动脉的特征性结构硬化。基质金属蛋白酶（Matrix metalloproteinases，MMPs）具有很强的蛋白水解活性，在基质更新中起着重要作用。在这里，我们使用Mmp 12 −/−小鼠来研究一种有效的金属弹性蛋白酶MMP-12对年轻和自然衰老小鼠胸主动脉和腹主动脉生物力学表型的影响。一个关键的发现是，编码MMP-12的基因（Mmp 12）的种系缺失改变了年轻成年小鼠的生物力学特性。因此，在主动脉老化过程中，野生型小鼠的生物力学性质的百分比变化大于MMP-12缺陷小鼠，尽管弹性储能和扩张性总体下降，计算的脉搏波速度增加。减少的弹性能量储存损害了主动脉增加顺行和逆行血流的能力，而增加的脉搏波速度会对终末器官产生不利影响，这两种情况都是人类主动脉老化的特征。总之，MMP-12是在主动脉中建立生物力学指标的稳态值的基础，并且其缺失导致年轻小鼠中的提前老化主动脉表型。
Mechanical homeostasis emerges following normal development of the arterial wall and requires thereafter a slow balanced degradation and deposition of extracellular matrix constituents within an unchanging mechanical state. Recent findings suggest that homeostasis is compromised in arterial aging, which contributes to the structural stiffening that is characteristic of aged central arteries. Matrix metalloproteinases (MMPs) have strong proteolytic activity and play fundamental roles in matrix turnover. Here, we use Mmp12−/− mice to examine effects of a potent metalloelastase, MMP-12, on the biomechanical phenotype of the thoracic and abdominal aorta in young and naturally aged mice. A key finding is that germline deletion of the gene (Mmp12) that encodes MMP-12 alters biomechanical properties from normal more in young adult than in older adult mice. Consequently, percent changes in biomechanical properties during aortic aging are greater in wild-type than in MMP-12 deficient mice, though with similar overall decreases in elastic energy storage and distensibility and increases in calculated pulse wave velocity. Reduced elastic energy storage compromises the ability of the aorta to augment antegrade and retrograde blood flow while an increased pulse wave velocity can adversely affect end organs, both conditions being characteristic of aortic aging in humans. In summary, MMP-12 is fundamental for establishing homeostatic values of biomechanical metrics in the aorta and its absence leads to a pre-aged aortic phenotype in young mice.
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影响因子：
2.4
作者：
Humphrey, J. D.;Eberth, J. F.;Dye, W. W.;Gleason, R. L.
通讯作者：
Gleason, R. L.
影响因子：
2.6
作者：
de Wit, Aletta;Vis, Kelly;Jeremy, Richmond W.
通讯作者：
Jeremy, Richmond W.
影响因子：
8
作者：
Liu, Shu-lin;Bajpai, Anamika;Assoian, Richard K.
通讯作者：
Assoian, Richard K.
影响因子：
6.2
作者：
Kielty, Cay M.
通讯作者：
Kielty, Cay M.
影响因子：
37.8
作者：
Luttun, A;Lutgens, E;Moons, L
通讯作者：
Moons, L