Distribution of shear stress over smooth muscle cells in deformable arterial wall.
ABSTRACT A biphasic, anisotropic model of the deformable aortic wall in combination with computational fluid dynamics is used to investigate the variation of shear stress over smooth muscle cells (SMCs) with transmural pressure. The media layer is modeled as a porous medium consisting of SMCs and a homogeneous porous medium of interstitial fluid and elastin, collagen and proteoglycans fibers. Interstitial fluid enters the media through fenestral pores, which are distributed over the internal elastic lamina (IEL). The IEL is considered as an impermeable barrier to fluid flow except at fenestral pores. The thickness and the radius of aortic wall vary with transmural pressure ranging from 10 to 180 mm Hg. It is assumed that SMCs are cylinders with a circular cross section at 0 mm Hg. As the transmural pressure increases, SMCs elongate with simultaneous change of cross sectional shape into ellipse according to the strain field in the media. Results demonstrate that the variation of shear stress within the media layer is significantly dependent on the configuration and cross sectional shape of SMCs. In the staggered array of SMCs, the shear stress over the first SMC nearest to the IEL is about 2.2 times lower than that of the square array. The shear stress even over the second nearest SMC to the IEL is considerably higher (about 15%) in the staggered array. In addition to configuration and cross sectional shape of SMCs, the variation of structural properties of the media layer with pressure and the sensitivity of the local shear stress to the minimum distance between SMCs and the IEL (reducing with transmural pressure) between SMCs and the IEL are studied. At 180 mm Hg, the ratio of the local shear stress of the nearest SMC to that of the second nearest SMC is 4.8 in the square array, whereas it reduces to about 1.8 in the staggered array. The importance of the fluid shear stress is associated with its role in the biomolecular state of smooth muscle cells bearing the shear stress.
- Biorheology 02/1980; 17(1-2):111-23. · 1.29 Impact Factor
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ABSTRACT: In this study, the shape and the configuration of smooth muscle cells (SMCs) within the arterial wall are altered to investigate their influence on molecular transport across the media layer of the thoracic aorta wall. In a 2D geometry of the media layer containing SMCs, the finite-element method has been employed to simulate the diffusion of solutes through the media layer. The media is modeled as a heterogeneous system composed of SMCs having elliptic or circular cross sections embedded in a homogeneous porous medium made of proteoglycan and collagen fibers with an interstitial fluid filling the void. The arrangement of SMCs is in either ordered or disordered fashion for different volume fractions of SMCs. The interstitial fluid enters the media through fenestral pores, which are assumed to be distributed uniformly over the internal elastic lamina (IEL). Results revealed that in an ordered arrangement of SMCs, the concentration of adenosine 5'-triphosphate (ATP) over the surface of SMCs with an elliptic cross section is 5-8% more than those of circular SMCs in volume fractions of 0.4-0.7. The ATP concentration at the SMC surface decreases with volume fraction in the ordered configuration of SMCs. In a disordered configuration, the local ATP concentration at the SMC surface and in the bulk are strongly dependent on the distance between neighboring SMCs, as well as the minimum distance between SMCs and fenestral pores. Moreover, the SMCs in farther distances from the IEL are as important as those just beneath the IEL in disordered configurations. The results of this study lead us to better understanding of the role of SMCs in controlling the diffusion of important species such as ATP within the arterial wall.Medical & Biological Engineering & Computing 12/2007; 45(11):1005-14. · 1.79 Impact Factor
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ABSTRACT: Vascular smooth muscle cell (SMC) migration is a hallmark of intimal hyperplasia (IH), the progression of which is affected by hemodynamic conditions at the diseased site. The realization that SMCs are exposed to blood flow in both denuded vessels (direct blood flow) and intact vessels (interstitial blood flow) motivated this study of the effects of fluid flow shear stress (SS) on SMC migration. Rat aortic SMCs were seeded onto Matrigel-coated cell culture inserts, and their migratory activity toward PDGF-BB when exposed to SS in a rotating disk apparatus was quantified. Four hours of either 10 or 20 dyn/cm2 SS significantly inhibited SMC migration to the bottom side of the insert. This inhibition was associated with downregulation of SMC matrix metalloproteinase (MMP)-2 activation. Four hours of 10 dyn/cm2 SS also drastically increased SMC production of NO. A NO synthase inhibitor (N(G)-nitro-L-arginine methyl ester; 100 microM) abolished the shear-induced increase in SMC NO production as well as the inhibition of migration and MMP-2 activity. A NO donor (S-nitroso-N-acetyl-penicillamine; 500 microM) suppressed SMC migration via the reduction of both total and active MMP-2 levels. Addition of 10 microM MMP-2 inhibitor I to inserts significantly reduced SMC migration. Western blots showed no effect of 4 h of 20 dyn/cm2 SS on SMC production of PDGF-AA, another chemical known to suppress SMC migration. Thus it appears that SS acts to suppress SMC migration by upregulating the cellular production of NO, which in turn inhibits MMP-2 activity.AJP Heart and Circulatory Physiology 06/2005; 288(5):H2244-52. · 3.63 Impact Factor