Diet alters age-related remodeling of aortic collagen in mice susceptible to atherosclerosis
Diet alters age-related remodeling of aortic collagen in mice susceptible to atherosclerosis
复制标题
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
DOI：
10.1152/ajpheart.00420.2020
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发表时间：
2021
影响因子：
4.8
通讯作者：
Lessner, Susan M.
中科院分区：
文献类型：
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作者：
Watson, Shana R.;Cooper, Kara M.;Liu, Piaomu;Gharraee, Nazli;Du, Liya;Han, Savannah M.;Peña, Edsel A.;Sutton, Michael A.;Eberth, John F.;Lessner, Susan M.
血管细胞重构细胞外基质以响应老化或机械负荷的变化。在这里，我们的特点是胶原蛋白的结构在年龄相关的主动脉重塑动脉粥样硬化倾向的小鼠。我们假设胶原纤维取向的变化反映了作用于动脉壁的被动力和主动力之间的平衡改变。我们研究了两个可以改变这种平衡的因素，内皮功能障碍和平滑肌细胞（SMC）收缩性降低。通过二次谐波显微镜观察6周龄和6月龄的普通饲料和7.5月龄的西方饲料（WD）的载脂蛋白E（apoE）基因敲除（KO）小鼠主动脉外膜中的胶原纤维组织，使用图像分析获得平均纤维取向。外膜胶原纤维变得更加明显的纵向取向与老化的apoE基因敲除小鼠的食物饮食。相反，在WD小鼠中，随着年龄的增长，纤维变得更加周向取向。总胶原含量随年龄增长而显著增加。我们比较了内皮型一氧化氮合酶和乙酰胆碱介导的一氧化氮释放的表达，但没有发现老年小鼠内皮功能障碍的证据。所有组的时间平均血流量均无显著变化。主动脉环的钢丝肌造影显示，主动应激生成随年龄的增加而减少，WD小鼠的主动应激生成显著加剧。我们的结论是，主动脉显示了一个独特的重塑反应致动脉粥样硬化的刺激，改变胶原组织。胶原重组可以在没有改变的血液动力学的情况下发生，并且可以代表对血管SMC产生的减少的主动应激的适应性反应。新的和值得注意的在该研究中进行了以下主要观察：1）在喂食普通食物的apoE敲除小鼠中，主动脉外膜胶原纤维随着年龄的增长变得更加纵向取向;2）相反地，在喂食高脂肪食物的apoE敲除小鼠中，外膜胶原纤维随着年龄的增长变得更加周向取向; 3）在高脂饮食的小鼠中，外膜胶原含量随着年龄的增长而显著增加;4）胶原组织的这些改变主要发生在没有血液动力学变化的情况下;以及5）在高脂饮食的老年小鼠中，胶原的周向重定向与主动力产生（收缩力）的降低有关。
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.NEW & NOTEWORTHYThe following major observations were made in this study:1) aortic adventitial collagen fibers become more longitudinally oriented with aging in apolipoprotein E knockout mice fed a chow diet;2) conversely, adventitial collagen fibers become more circumferentially oriented with aging in apoE knockout mice fed a high-fat diet;3) adventitial collagen content increases significantly with age in mice on a high-fat diet;4) these alterations in collagen organization occur largely in the absence of hemodynamic changes; and5) circumferential reorientation of collagen is associated with decreased active force generation (contractility) in aged mice on a high-fat diet.