Heterogeneous transmural proteoglycan distribution provides a mechanism for regulating residual stresses in the aorta
Heterogeneous transmural proteoglycan distribution provides a mechanism for regulating residual stresses in the aorta
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DOI：
10.1152/ajpheart.01027.2007
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发表时间：
2008-03-01
影响因子：
4.8
通讯作者：
Costa, Kevin D.
中科院分区：
文献类型：
--
作者：
Azeloglu, Evren U.;Albro, Michael B.;Costa, Kevin D.
动脉壁含有大量带电蛋白多糖，其分布不均匀，在内膜和内层浓度最高。本研究的假设是蛋白聚糖的跨壁分布在调节动脉壁残余应力中起重要作用。首先利用带电水合组织的混合理论框架对这一假设进行了理论验证，然后通过测量不同离子强度NaCl溶液中大鼠主动脉的开口角进行了实验验证。利用固体基质剪切模量和蛋白聚糖固定电荷密度的真实值，建立了主动脉环的三维有限元模型，得出了与文献报道值相当的开口角和渗透压变化。实验中，等渗盐水（300 mosM）的平均开口角为15 +/- 17度，高渗（2000 mosM）和低渗（0 mosM）条件下的平均开口角分别为4 +/- 19度和73 +/- 18度（n=16）。此外，等渗（300 mosM）蔗糖（一种不带电的分子）的开口角为60 +/- 16度（n=11），表明电荷效应，而不是细胞膨胀，是这些观察结果的主要潜在机制。在渗透挑战下开放角度的变化程度表明，固定电荷密度的跨壁异质性在控制主动脉零应力结构中起着至关重要的作用。这一发现的一个重要意义是，动脉壁重构可能通过改变蛋白聚糖在壁厚上的沉积而发生，从而为调节血管组织的机械稳态提供了一种新的机制。
The arterial wall contains a significant amount of charged proteoglycans, which are inhomogeneously distributed, with the greatest concentrations in the intimal and medial layers. The hypothesis of this study is that the transmural distribution of proteoglycans plays a significant role in regulating residual stresses in the arterial wall. This hypothesis was first tested theoretically, using the framework of mixture theory for charged hydrated tissues, and then verified experimentally by measuring the opening angle of rat aorta in NaCl solutions of various ionic strengths. A three-dimensional finite element model of aortic ring, using realistic values of the solid matrix shear modulus and proteoglycan fixed-charge density, yielded opening angles and changes with osmolarity comparable to values reported in the literature. Experimentally, the mean opening angle in isotonic saline (300 mosM) was 15 +/- 17 degrees and changed to 4 +/- 19 degrees and 73 +/- 18 degrees under hypertonic (2,000 mosM) and hypotonic (0 mosM) conditions, respectively (n=16). In addition, the opening angle in isotonic (300 mosM) sucrose, an uncharged molecule, was 60 +/- 16 degrees (n=11), suggesting that the charge effect, not cellular swelling, was the major underlying mechanism for these observations. The extent of changes in opening angle under osmotic challenges suggests that transmural heterogeneity of fixed-charge density plays a crucial role in governing the zero-stress configuration of the aorta. A significant implication of this finding is that arterial wall remodeling in response to altered wall stresses may occur via altered deposition of proteoglycans across the wall thickness, providing a novel mechanism for regulating mechanical homeostasis in vascular tissue.