Elastin haploinsufficiency accelerates age-related structural and functional changes in the renal microvasculature and impairment of renal hemodynamics in female mice.
Elastin haploinsufficiency accelerates age-related structural and functional changes in the renal microvasculature and impairment of renal hemodynamics in female mice.
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DOI：
10.3389/fphys.2023.1141094
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发表时间：
2023
影响因子：
4
通讯作者：
中科院分区：
文献类型：
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弹性蛋白的功能性下降与动脉僵硬度增加有关，这是发生心血管疾病的已知风险因素。虽然弹性蛋白不足对管道动脉硬化的贡献已得到充分描述，但对阻力血管系统的结构和功能的影响知之甚少，阻力血管系统有助于总外周阻力和器官灌注的调节。在这项研究中，我们确定了弹性蛋白功能不全如何影响与年龄相关的肾脏微血管结构和生物力学特性的变化，改变肾脏血流动力学和肾血管床对雌性小鼠肾脏灌注压（RPP）变化的反应。使用多普勒超声，我们发现，阻力指数和脉动指数在年轻的Eln +/−和老年小鼠升高。组织学检查显示，年轻Eln +/−和老年小鼠肾脏的肾内小动脉中，内外弹性层变薄，伴随着中层弹性蛋白碎片增加，无任何钙沉积。叶间动脉的压力肌电图显示，年轻Eln +/−和老年小鼠的血管在压力负荷期间扩张性略有下降，但在压力卸载时血管回缩效率大幅下降。为了检查肾脏微血管结构变化是否影响肾脏血流动力学，我们通过同时闭塞上级肠系膜动脉和腹腔动脉来阻断神经体液输入并增加肾脏灌注压。肾灌注压增加导致所有组的血压发生强烈变化;然而，在年轻的Eln +/−和老年小鼠中，肾血管阻力和肾血流量（RBF）的变化变钝，伴有自动调节指数降低，表明肾自动调节功能受损更严重。最后，老年Eln +/−小鼠的脉压增加与高肾血流量呈正相关。总之，我们的数据表明，弹性蛋白的损失对肾脏微血管的结构和功能完整性产生负面影响，最终恶化与年龄相关的肾功能下降。
Age-related decline in functional elastin is associated with increased arterial stiffness, a known risk factor for developing cardiovascular disease. While the contribution of elastin insufficiency to the stiffening of conduit arteries is well described, little is known about the impact on the structure and function of the resistance vasculature, which contributes to total peripheral resistance and the regulation of organ perfusion. In this study, we determined how elastin insufficiency impinges on age-related changes in the structure and biomechanical properties of the renal microvasculature, altering renal hemodynamics and the response of the renal vascular bed to changes in renal perfusion pressure (RPP) in female mice. Using Doppler ultrasonography, we found that resistive index and pulsatility index were elevated in young Eln +/− and aged mice. Histological examination showed thinner internal and external elastic laminae, accompanied by increased elastin fragmentation in the medial layer without any calcium deposits in the small intrarenal arteries of kidneys from young Eln +/− and aged mice. Pressure myography of interlobar arteries showed that vessels from young Eln +/− and aged mice had a slight decrease in distensibility during pressure loading but a substantial decline in vascular recoil efficiency upon pressure unloading. To examine whether structural changes in the renal microvasculature influenced renal hemodynamics, we clamped neurohumoral input and increased renal perfusion pressure by simultaneously occluding the superior mesenteric and celiac arteries. Increased renal perfusion pressure caused robust changes in blood pressure in all groups; however, changes in renal vascular resistance and renal blood flow (RBF) were blunted in young Eln +/− and aged mice, accompanied by decreased autoregulatory index, indicating greater impairment of renal autoregulation. Finally, increased pulse pressure in aged Eln +/− mice positively correlated with high renal blood flow. Together, our data show that the loss of elastin negatively affects the structural and functional integrity of the renal microvasculature, ultimately worsening age-related decline in kidney function.
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影响因子：
2.5
作者：
Jie L;Owens EA;Plante LA;Fang Z;Rensing DT;Moeller KD;Osei-Owusu P
通讯作者：
Osei-Owusu P
DOI：
10.1152/ajpregu.00766.2002
发表时间：
2003-09-01
影响因子：
2.8
作者：
Just, A;Arendshorst, WJ
通讯作者：
Arendshorst, WJ
影响因子：
5.6
作者：
Feihl, Francois;Liaudet, Lucas;Waeber, Bernard
通讯作者：
Waeber, Bernard
影响因子：
15.9
作者：
Faury, G;Pezet, M;Mecham, RP
通讯作者：
Mecham, RP
影响因子：
10.8
作者：
Chung, Ada W. Y.;Yang, H. H. Clarice;Levin, Adeera
通讯作者：
Levin, Adeera