Matrix metalloproteinase-2 and -9 are associated with high stresses predicted using a nonlinear heterogeneous model of arteries.
Matrix metalloproteinase-2 and -9 are associated with high stresses predicted using a nonlinear heterogeneous model of arteries.
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DOI：
10.1115/1.3005163
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发表时间：
2009-01
期刊：
影响因子：
--
通讯作者：
Vito RP
中科院分区：
文献类型：
--
作者：
Kim YS;Galis ZS;Rachev A;Han HC;Vito RP
Arteries adapt to their mechanical environment by undergoing remodeling of the structural scaffold via the action of matrix metalloproteinases (MMPs). Cell culture studies have shown that stretching vascular smooth muscle cells (VSMCs) positively correlates to the production of MMP-2 and -9. In tissue level studies, the expression and activation of MMP-2 and -9 are generally higher in the outer media. However, homogeneous mechanical models of arteries predict lower stress and strain in the outer media, which appears inconsistent with experimental findings. The effects of heterogeneity may be important to our understanding of VSMC function, since arteries exhibit structural heterogeneity across the wall. We hypothesized that local stresses, computed using a heterogeneous mechanical model of arteries, positively correlate to the levels of MMP-2 and -9 in situ. We developed a model of the arterial wall accounting for nonlinearity, residual strain, anisotropy, and structural heterogeneity. The distributions of elastin and collagen fibers in situ, measured in the media of porcine carotid arteries, showed significant non-uniformities. Anisotropy was represented by the direction of collagen fibers measured by the helical angle of VSMC nuclei. The points at which the collagen fibers became load bearing were computed assuming a uniform fiber strain and orientation under physiological loading conditions; an assumption motivated by morphological measurements. The distributions of circumferential stresses, computed using both heterogeneous and homogeneous models, were correlated to the distributions of expression and activation of MMP-2 and -9 in porcine common carotid arteries incubated in an ex vivo perfusion organ culture system under physiological conditions for 48 hours. While strains computed using incompressibility were identical in both models, the heterogeneous model, unlike the homogeneous model, predicted higher circumferential stresses in the outer layer correlated to the expressions and activations of MMP-2 and -9. This implies that localized remodeling occurs in the areas of high stress and agrees with results from cell culture studies. The results support the role of mechanical stress in vascular remodeling and the importance of structural heterogeneity in understanding mechanobiological responses.
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DOI：
10.1016/0006-291x(67)90316-6
发表时间：
1967-01-01
影响因子：
3.1
作者：
BLOMFIELD, J;FARRAR, JF
通讯作者：
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影响因子：
10.8
作者：
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通讯作者：
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DOI：
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发表时间：
1991-05-01
期刊：
ARTERIOSCLEROSIS AND THROMBOSIS
影响因子：
--
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通讯作者：
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DOI：
10.1115/1.3138417
发表时间：
1983-01-01
影响因子：
1.7
作者：
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通讯作者：
FUNG, YC
DOI：
10.1152/ajpheart.1999.277.5.h2002
发表时间：
1999-11-01
影响因子：
4.8
作者：
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通讯作者：
Galis, ZS