Evolving structure-function relations during aortic maturation and aging revealed by multiphoton microscopy.

Evolving structure-function relations during aortic maturation and aging revealed by multiphoton microscopy.
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多光子显微镜揭示主动脉成熟和衰老过程中不断演变的结构 - 功能关系

DOI:
10.1016/j.mad.2021.111471
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发表时间:
2021-06
影响因子:
5.3
通讯作者:
Humphrey JD
Humphrey JD
中科院分区:
医学3区
文献类型:
--
作者:
Cavinato C;Murtada SI;Rojas A;Humphrey JD

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促进主动脉内稳态的不断演变的微观结构和机械特性是年龄特异性适应和疾病进展的基础。我们结合联合收割机离体多光子显微镜和双轴生物力学表型定量和相关的层特异性的微观结构参数,为主要的细胞外基质成分(纤维胶原蛋白和弹性层)和细胞(内皮,平滑肌和外膜),从断奶到自然老化长达一年的小鼠主动脉的机械性能。老化内皮的特征在于细胞密度的进行性降低和细胞取向的改变。中膜同样显示平滑肌细胞密度和排列进行性降低,但从中期到老年,层间增宽,表明细胞肥大、基质蓄积或两者兼而有之。尽管组织厚度没有变化,但老化外膜显示胶原纤维束明显增厚和变直,细胞密度降低,提示与年龄相关的重塑而非生长。多个微观结构的变化与年龄相关的周向和轴向材料刚度的增加,以及其他机械指标。由于衰老作为心血管疾病危险因素的重要性,在评估叠加的疾病相关变化作为发病年龄的函数时,了解结构和功能变化的正常进展至关重要。
The evolving microstructure and mechanical properties that promote homeostasis in the aorta are fundamental to age-specific adaptations and disease progression. We combine ex vivo multiphoton microscopy and biaxial biomechanical phenotyping to quantify and correlate layer-specific microstructural parameters, for the primary extracellular matrix components (fibrillar collagen and elastic lamellae) and cells (endothelial, smooth muscle, and adventitial), with mechanical properties of the mouse aorta from weaning through natural aging up to one year. The aging endothelium was characterized by progressive reductions in cell density and altered cellular orientation. The media similarly showed a progressive decrease in smooth muscle cell density and alignment though with inter-lamellar widening from intermediate to older ages, suggesting cell hypertrophy, matrix accumulation, or both. Despite not changing in tissue thickness, the aging adventitia exhibited a marked thickening and straightening of collagen fiber bundles and reduction in cell density, suggestive of age-related remodeling not growth. Multiple microstructural changes correlated with age-related increases in circumferential and axial material stiffness, among other mechanical metrics. Because of the importance of aging as a risk factor for cardiovascular diseases, understanding the normal progression of structural and functional changes is essential when evaluating superimposed disease-related changes as a function of the age of onset.
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