Effect of substrate stiffness and PDGF on the behavior of vascular smooth muscle cells: Implications for atherosclerosis

Brown, Xin Q.; Bartolák‐Suki, Erzsébet; Williams, Corin; Walker, Mathew L.; Weaver, Valerie M.; Wong, Joyce Y.

doi:10.1002/jcp.22202

Cited by 86 publications

(82 citation statements)

References 53 publications

(69 reference statements)

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“…Our finding suggesting that local wall stiffness plays a role in the initiation of atherosclerosis lesions appears to be in agreement with other clinical (1,32), biological (2,10), and animal (42) studies. Interestingly, the animal study performed by Van Herck et al (42) showed that an increase of arterial stiffness promotes plaque development.…”

Section: Discussionsupporting

confidence: 93%

Is arterial wall-strain stiffening an additional process responsible for atherosclerosis in coronary bifurcations?: an in vivo study based on dynamic CT and MRI

Ohayon

Gharib

García

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Coronary bifurcations represent specific regions of the arterial tree that are susceptible to atherosclerotic lesions. While the effects of vessel compliance, curvature, pulsatile blood flow, and cardiac motion on coronary endothelial shear stress have been widely explored, the effects of myocardial contraction on arterial wall stress/strain (WS/S) and vessel stiffness distributions remain unclear. Local increase of vessel stiffness resulting from wall-strain stiffening phenomenon (a local process due to the nonlinear mechanical properties of the arterial wall) may be critical in the development of atherosclerotic lesions. Therefore, the aim of this study was to quantify WS/S and stiffness in coronary bifurcations and to investigate correlations with plaque sites. Anatomic coronary geometry and cardiac motion were generated based on both computed tomography and MRI examinations of eight patients with minimal coronary disease. Computational structural analyses using the finite element method were subsequently performed, and spatial luminal arterial wall stretch (LWStretch) and stiffness (LWStiff) distributions in the left main coronary bifurcations were calculated. Our results show that all plaque sites were concomitantly subject to high LW Stretch and high LWStiff, with mean amplitudes of 34.7 Ϯ 1.6% and 442.4 Ϯ 113.0 kPa, respectively. The mean LW Stiff amplitude was found slightly greater at the plaque sites on the left main coronary artery (mean value: 482.2 Ϯ 88.1 kPa) compared with those computed on the left anterior descending and left circumflex coronary arteries (416.3 Ϯ 61.5 and 428.7 Ϯ 181.8 kPa, respectively). These findings suggest that local wall stiffness plays a role in the initiation of atherosclerotic lesions. atherosclerosis; coronary disease; wall stiffness; wall stress; biomechanics; computed tomography; magnetic resonance imaging ATHEROSCLEROSIS is a chronic inflammatory disease with systemic manifestations (12,30). Although the coronary and peripheral systems in their entirety are exposed to the same atherogenic cells and molecules in the plasma, atherosclerotic lesions form at specific regions of the arterial tree. Such lesions appear in the vicinity of branch points, the outer wall of bifurcations, and the inner wall of curves (8,18,43). In a pathological study of human coronary lesions, Kolodgie et al. (24) found that healed plaque ruptures were predominantly found in the proximal portions of the left anterior descending (LAD), right coronary (RCA), left circumflex (LCx), and left main (LM) arteries.The coronary arterial wall is constantly subjected to both flow-induced shear stress and wall strain/stress (WS/S) by blood pressure and myocardial contraction. Low or oscillatory endothelial shear stress (ESS) is not the only mechanical stimulus that promotes the inflammatory process by inducing an oxidative response in vascular endothelial cells (ECs) (27). Several biological studies (26, 28, 29) performed on cultured ECs have reported that, above an endothelial cyclic stretch threshold o...

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Section: Discussionsupporting

confidence: 93%

Is arterial wall-strain stiffening an additional process responsible for atherosclerosis in coronary bifurcations?: an in vivo study based on dynamic CT and MRI

Ohayon

Gharib

García

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…It is an important factor in inducing SMC proliferation and migration from arterial media to intima. Therefore, inhibiting the migration and proliferation of VSMC by suppressing the PDGF expression is also a new target for treatment of AS in recent years [20][21][22] . This study showed that puerarin inhibited the expression of PCNA and PDGF in rabbits in the pathological process of AS, decrease SMC proliferation, and significantly reduce the formation of plaque.…”

Section: Discussionmentioning

confidence: 99%

The anti-atherosclerotic effects of puerarin on induced-atherosclerosis in rabbits

Liu

Zhang²,

Wei³

et al. 2015

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background. Cardiovascular disease is a major health issue worldwide, which has been well treated by the extracts of traditional herbs. Radix Puerariae, the dried root of the leguminous plant Pueraria lobata (Willd.) Ohwi, is a delicious vegetable in some southern provinces of China. Puerarin has also been widely used to treat human diseases, but few controlled studies are available. Aim. To determine the anti-atherosclerotic effects of puerarin on fat diet-induced atherosclerosis (AS) in rabbits.Methods. An AS model was established by feeding 60 rabbits a high-fat diet and randomly dividing them into 6 groups: (1) normal control, (2) a model group (3) the statin, simvastatin and groups (4), (5) and (6) received 3 different amounts of puerarin. The fasting sera of all animals were collected before and after 90 days treatment to determine the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and high density lipoproteincholesterol (HDL-C). The aortas were pathomorphologically examined. PCNA and PDGF-A protein levels were assessed by Western blot. Results. On the 90th day, the levels of TC, TG and LDL-C were significantly lower in high-and middle-dose puerarin groups and simvastatin group than in the model group (P<0.05), and the HDL-C level was higher. The percentages of plaque area to the total aortic area differed significantly for high-and middle-dose puerarin groups, simvastatin group and model group (P<0.05). Whole blood viscosity increased in the high-fat diet groups, while those in the treatment groups (except for the low-dose puerarin group) were significantly lower than those in the model group (P<0.05). PCNA and PDGF-A protein expression levels of rabbit aorta were low in the normal group. Protein expression levels in the groups fed the high-fat diet were significantly increased (P<0.05), but those in the high-dose puerarin group and simvastatin group were significantly decreased compared with the model group (P<0.05). Conclusions. Puerarin inhibits the formation and development of AS plaque and suppresses the migration and reproduction of vascular smooth muscle cells by decreasing PCNA and PDGF-A expressions in the rabbit. This is encouraging in terms of cardiovascular disease prevention/treatment.

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“…The degradation in the collagen stiffness is not as pronounced in the native specimens, whereby the collagen retains 60% of it mechanical stiffness in comparison to the unheated controls. Potentially this stiffness reduction may have negative implications if repopulation of smooth muscle cells occurs, as Brown et al (2010) demonstrated that a reduction to 61% of the native tissue's stiffness value caused vascular smooth muscle cells not to survive overnight in tissue culture on these reduced stiffness substrates. However, they also demonstrated that proliferation on an even stiffer substrate was far greater, a 4.5 fold increase in proliferation was observed in comparison to the native stiffness mimicking substrate.…”

Section: Discussionmentioning

confidence: 99%

The effect of a thermal renal denervation cycle on the mechanical properties of the arterial wall

Hopkins

Sheridan

Sharif

et al. 2014

Journal of Biomechanics

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a b s t r a c tThe aim of this study was to determine the effect that a thermal renal denervation cycle has on the mechanical properties of the arterial wall. Porcine arterial tissue specimens were tested in three groups: native tissue, decellularized tissue, decellularized with collagen digestion (e.g. elastin only). One arterial specimen was used as an unheated control specimen while another paired specimen was subjected to a thermal cycle of 70 1C for 120 s (n ¼10). The specimens were subjected to tensile loading and a shrinkage analysis. We observed two key results: The mechanical properties associated with the elastin extracellular matrix (ECM) were not affected by the thermal cycle. The effect of the thermal cycle on the collagen (ECM) was significant, in both the native and decellularized groups the thermal cycle caused a statistically significant decrease in stiffness, and failure strength, moreover the native tissue demonstrated a 27% reduction in lumen area post exposure to the thermal cycle. We have demonstrated that a renal denervation thermal cycle can significantly affect the mechanical properties of an arterial wall, and these changes in stiffness and failure strength were associated with alterations to the collagen rather than the elastin extracellular matrix component.

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Effect of substrate stiffness and PDGF on the behavior of vascular smooth muscle cells: Implications for atherosclerosis

Cited by 86 publications

References 53 publications

Is arterial wall-strain stiffening an additional process responsible for atherosclerosis in coronary bifurcations?: an in vivo study based on dynamic CT and MRI

Is arterial wall-strain stiffening an additional process responsible for atherosclerosis in coronary bifurcations?: an in vivo study based on dynamic CT and MRI

The anti-atherosclerotic effects of puerarin on induced-atherosclerosis in rabbits

The effect of a thermal renal denervation cycle on the mechanical properties of the arterial wall

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