Aging and associated progressive arterial stiffening are both important predictors for the development of cardiovascular diseases. Recent evidence showed that autophagy, a catabolic cellular mechanism responsible for nutrient recycling, plays a major role in the physiology of vascular cells such as endothelial cells and vascular smooth muscle cells (VSMCs). Moreover, several autophagy inducing compounds are effective in treating arterial stiffness. Yet, a direct link between VSMC autophagy and arterial stiffness remains largely unidentified. Therefore, we investigated the effects of a VSMC-specific deletion of the essential autophagy-related gene Atg7 in young mice (3.5 months) (Atg7^F/F SM22α-Cre⁺ mice) on the biomechanical properties of the aorta, using an in-house developed Rodent Oscillatory Tension Set-up to study Arterial Compliance (ROTSAC). Aortic segments of Atg7^F/F SM22α-Cre⁺ mice displayed attenuated compliance and higher arterial stiffness, which was more evident at higher distention pressures. Passive aortic wall remodeling, rather than differences in VSMC tone, is responsible for these phenomena, since differences in compliance and stiffness between Atg7^+/+ SM22α-Cre⁺ and Atg7^F/F SM22α-Cre⁺ aortas were more pronounced when VSMCs were completely relaxed by the addition of exogenous nitric oxide. These observations are supported by histological data showing a 13% increase in medial wall thickness and a 14% decrease in elastin along with elevated elastin fragmentation. In addition, expression of the calcium-binding protein S100A4, which is linked to matrix remodeling, was elevated in aortic segments of Atg7^F/F SM22α-Cre⁺ mice. Overall, these findings illustrate that autophagy exerts a crucial role in defining arterial wall compliance.

衰老和相关的进行性动脉硬化都是心血管疾病发展的重要预测指标。最近的证据表明自噬是负责营养循环的分解代谢细胞机制，在诸如内皮细胞和血管平滑肌细胞（VSMC）的血管细胞的生理学中起着重要作用。此外，几种自噬诱导化合物可有效治疗动脉僵硬。然而，VSMC自噬与动脉僵硬度之间的直接联系在很大程度上尚不清楚。因此，我们研究了VSMC特异性缺失必需自噬相关基因Atg7在年轻小鼠（3.5个月）中的作用（Atg7 ^{F /} FSM22α -Cre ⁺使用内部开发的啮齿动物振荡张力装置研究主动脉的顺应性（ROTSAC），了解主动脉的生物力学特性。Atg7 ^{F /} FSM22α -Cre ⁺小鼠的主动脉节段显示顺应性减弱和较高的动脉僵硬度，在较高的扩张压力下更明显。被动主动脉壁重塑，而不是VSMC的色调差，负责这些现象，因为在ATG7之间的合规性和刚度的差异^{+ / +} SM22αCre重组⁺和ATG7 ^{F / F} SM22αCre重组⁺当通过添加外源一氧化氮使VSMC完全放松时，主动脉更加明显。这些观察结果得到组织学数据的支持，组织学数据显示，内壁厚度增加了13％，弹性蛋白减少了14％，同时弹性蛋白的碎片增多。此外，与基质重塑有关的钙结合蛋白S100A4的表达在Atg7 ^{F /} FSM22α -Cre ⁺小鼠的主动脉节段中升高。总体而言，这些发现表明自噬在定义动脉壁顺应性中起着至关重要的作用。