Vascular cells restructure extracellular matrix in response to aging or changes in mechanical loading. Here, we characterized collagen architecture during age-related aortic remodeling in atherosclerosis-prone mice. We hypothesized that changes in collagen fiber orientation reflect an altered balance between passive and active forces acting on the arterial wall. We examined two factors that can alter this balance, endothelial dysfunction and reduced smooth muscle cell (SMC) contractility. Collagen fiber organization was visualized by second-harmonic generation microscopy in aortic adventitia of apolipoprotein E (apoE) knockout (KO) mice at 6 wk and 6 mo of age on a chow diet and at 7.5 mo of age on a Western diet (WD), using image analysis to yield mean fiber orientation. Adventitial collagen fibers became significantly more longitudinally oriented with aging in apoE knockout mice on chow diet. Conversely, fibers became more circumferentially oriented with aging in mice on WD. Total collagen content increased significantly with age in mice fed WD. We compared expression of endothelial nitric oxide synthase and acetylcholine-mediated nitric oxide release but found no evidence of endothelial dysfunction in older mice. Time-averaged volumetric blood flow in all groups showed no significant changes. Wire myography of aortic rings revealed decreases in active stress generation with age that were significantly exacerbated in WD mice. We conclude that the aorta displays a distinct remodeling response to atherogenic stimuli, indicated by altered collagen organization. Collagen reorganization can occur in the absence of altered hemodynamics and may represent an adaptive response to reduced active stress generation by vascular SMCs.

中文翻译：

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饮食改变易患动脉粥样硬化的小鼠与年龄相关的主动脉胶原蛋白重塑


血管细胞响应衰老或机械负荷的变化而重组细胞外基质。在这里，我们表征了易患动脉粥样硬化的小鼠与年龄相关的主动脉重塑过程中的胶原蛋白结构。我们假设胶原纤维方向的变化反映了作用于动脉壁的被动力和主动力之间平衡的改变。我们检查了两个可以改变这种平衡的因素，即内皮功能障碍和平滑肌细胞（SMC）收缩力降低。通过二次谐波产生显微镜观察载脂蛋白 E (apoE) 敲除 (KO) 小鼠主动脉外膜中的胶原纤维组织，小鼠在 6 周和 6 月龄时采用食物饮食，在 7.5 月龄时采用西方饮食 (WD) ，使用图像分析得出平均纤维取向。在 apoE 基因敲除小鼠中，随着年龄的增长，外膜胶原纤维的纵向取向明显增强。相反，随着 WD 小鼠年龄的增长，纤维变得更加圆周定向。喂食 WD 的小鼠中，总胶原蛋白含量随着年龄的增长而显着增加。我们比较了内皮一氧化氮合酶的表达和乙酰胆碱介导的一氧化氮释放，但没有发现老年小鼠内皮功能障碍的证据。所有组的时间平均体积血流量均未显示显着变化。主动脉环的钢丝肌动描记显示，随着年龄的增长，主动应激产生减少，在 WD 小鼠中这种情况显着加剧。我们得出的结论是，主动脉对致动脉粥样硬化的刺激表现出明显的重塑反应，这通过胶原组织的改变来表明。胶原蛋白重组可以在血流动力学没有改变的情况下发生，并且可能代表对血管 SMC 产生的主动应激减少的适应性反应。