Changes in connective tissue colloidal charge density with atherosclerosis and age

Porterfield, SP; Calhoon, T. B.; Hs, Weiss

doi:10.1152/ajplegacy.1968.215.2.324

Cited by 13 publications

(12 citation statements)

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“…Hence, based on the most relevant data (Porterfield et al 1968; Chahine et al 2005; Azeloglu et al 2008), we performed parametric studies to investigate the potential role of inclusion stiffness (e.g., a neo-Hookean shear modulus of 0 kPa for a void and from 0.05 to 5.0 kPa for a GAG/PG pool) and fixed charge density (0 mEq/l for a void and from −50 mEq/l at baseline to −160 mEq/l). Figure 6 suggests that, over the range studied, the value of the GAG/PG stiffness had little effect on the predicted stress concentrations, whereas the value of the fixed charge density (i.e., Donnan swelling potential) had a dramatic effect, particularly on the value of the peak tensile radial stress just in front of the tip of the inclusion.…”

Section: Computational Resultsmentioning

confidence: 99%

“…Yet, the GAGs/PGs of interest are highly negatively charged, thus the more important simulations focused on this aspect of the overall mechanics. Given the lack of data on the electrochemistry of GAGs/PGs in TAADs, we selected parameter values that represented reasonable ranges of fixed charge density based on data that are available for the aorta (Porterfield et al 1968; Azeloglu et al 2008) as well as comparable experimental information on solutions of chondroitin sulfate (Chahine et al 2005). For values of fixed charge density ranging from −50 to −160 mEq/l, our simulations suggested that a Donnan swelling pressure could increase the in-plane stress concentrations, but even more so could increase the tensile radial stress locally, with values ranging from 40 to 100 kPa (relative to baseline values of −6 kPa).…”

Section: Discussionmentioning

confidence: 99%

“…The analysis was then performed via four sequential loading steps: a displacement-driven problem to impose initial equibiaxial circumferential and axial stresses of 100 kPa, a radial compression to superimpose a −6 kPa radial stress, an osmotic loading to increase the fixed charge density of the normal arterial wall from 0 mEq/l to its baseline value of −50 mEq/l (Porterfield et al 1968), and an osmotic loading of the inclusion to 0 (for a void) −80, or −160 mEq/l depending on the simulation. The one exception to this general strategy was the initial loading of the media to biaxial stresses of 240 kPa (circumferential) and 150 kPa (axial) for the case of elevated blood pressure (radial stress of −10 kPa).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Biomechanical roles of medial pooling of glycosaminoglycans in thoracic aortic dissection

Roccabianca

Ateshian

Humphrey

2013

Biomech Model Mechanobiol

102

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Spontaneous dissection of the human thoracic aorta is responsible for significant morbidity and mortality, yet this devastating biomechanical failure process remains poorly understood. In this paper, we present finite element simulations that support a new hypothesis for the initiation of aortic dissections that is motivated by extensive histopathological observations. Specifically, our parametric simulations show that the pooling of glycosaminoglycans/proteoglycans that is singularly characteristic of the compromised thoracic aorta in aneurysms and dissections can lead to significant stress concentrations and intra-lamellar Donnan swelling pressures. We submit that these localized increases in intramural stress may be sufficient both to disrupt the normal cell-matrix interactions that are fundamental to aortic homeostasis and to delaminate the layered microstructure of the aortic wall and thereby initiate dissection. Hence, pathologic pooling of glycosaminoglycans/proteoglycans within the medial layer of the thoracic aortic should be considered as a possible target for clinical intervention.

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Section: Computational Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Biomechanical roles of medial pooling of glycosaminoglycans in thoracic aortic dissection

Roccabianca

Ateshian

Humphrey

2013

Biomech Model Mechanobiol

102

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“…Hence, although the present results should hold qualitatively for any elastic artery, our use of data from the mouse carotid was dictated primarily by the availability of relevant data. There is a pressing need, therefore, to perform similar studies based directly on data for the thoracic aorta, which has, for example, a higher basal FCD than the abdominal aorta [30] and a higher propensity to dissect spontaneously [8].…”

Section: Discussionmentioning

confidence: 99%

Computational modelling suggests good, bad and ugly roles of glycosaminoglycans in arterial wall mechanics and mechanobiology

Roccabianca

Bellini

Humphrey

2014

J. R. Soc. Interface.

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The medial layer of large arteries contains aggregates of the glycosaminoglycan hyaluronan and the proteoglycan versican. It is increasingly thought that these aggregates play important mechanical and mechanobiological roles despite constituting only a small fraction of the normal arterial wall. In this paper, we offer a new hypothesis that normal aggregates of hyaluronan and versican pressurize the intralamellar spaces, and thereby put into tension the radial elastic fibres that connect the smooth muscle cells to the elastic laminae, which would facilitate mechanosensing. This hypothesis is supported by novel computational simulations using two complementary models, a mechanistically based finite-element mixture model and a phenomenologically motivated continuum hyperelastic model. That is, the simulations suggest that normal aggregates of glycosaminoglycans/proteoglycans within the arterial media may play equally important roles in supporting (i.e. a structural role) and sensing (i.e. an instructional role) mechanical loads. Additional simulations suggest further, however, that abnormal increases in these aggregates, either distributed or localized, may over-pressurize the intralamellar units. We submit that these situations could lead to compromised mechanosensing, anoikis and/or reduced structural integrity, each of which represent fundamental aspects of arterial pathologies seen, for example, in hypertension, ageing and thoracic aortic aneurysms and dissections.

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“…In particular, it is well known that the arterial wall contains a significant amount of proteoglycans and that these are inhomogeneously distributed across the arterial wall (Wight and Ross, 1975;Yao et al, 1994). Less well-known is that they carry a significant amount of negative charge (Porterfield et al, 1968). It is entirely plausible that this inhomogeneous fixed charge distribution plays a significant role in regulating the wellrecognized residual stresses across the arterial wall (Fung, 1990;, particularly since the synthesis of proteoglycans by arterial smooth muscle cells is known to be regulated by their strain environment (Lee etal, 2001).…”

Section: Discussionmentioning

confidence: 99%

On the theory of reactive mixtures for modeling biological growth

Ateshian

2007

Biomech Model Mechanobiol

183

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Mixture theory, which can combine continuum theories for the motion and deformation of solids and fluids with general principles of chemistry, is well suited for modeling the complex responses of biological tissues, including tissue growth and remodeling, tissue engineering, mechanobiology of cells and a variety of other active processes. A comprehensive presentation of the equations of reactive mixtures of charged solid and fluid constituents is lacking in the biomechanics literature. This study provides the conservation laws and entropy inequality, as well as interface jump conditions, for reactive mixtures consisting of a constrained solid mixture and multiple fluid constituents. The constituents are intrinsically incompressible and may carry an electrical charge. The interface jump condition on the mass flux of individual constituents is shown to define a surface growth equation, which predicts deposition or removal of material points from the solid matrix, complementing the description of volume growth described by the conservation of mass. A formu-lation is proposed for the reference configuration of a body whose material point set varies with time. State variables are defined which can account for solid matrix volume growth and remodeling. Constitutive constraints are provided on the stresses and momentum supplies of the various constituents, as well as the interface jump conditions for the electrochem cal potential of the fluids. Simplifications appropriate for biological tissues are also proposed, which help reduce the governing equations into a more practical format. It is shown that explicit mechanisms of growth-induced residual stresses can be predicted in this framework.

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Changes in connective tissue colloidal charge density with atherosclerosis and age

Cited by 13 publications

References 0 publications

Biomechanical roles of medial pooling of glycosaminoglycans in thoracic aortic dissection

Biomechanical roles of medial pooling of glycosaminoglycans in thoracic aortic dissection

Computational modelling suggests good, bad and ugly roles of glycosaminoglycans in arterial wall mechanics and mechanobiology

On the theory of reactive mixtures for modeling biological growth

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