A new flow co-culture system for studying mechanobiology effects of pulse flow waves

Scott-Drechsel, Devon E.; Su, Zhenbi; Hunter, Kendall S.; Li, Min; Shandas, Robin; Tan, Wei

doi:10.1007/s10616-012-9445-2

Cited by 22 publications

(31 citation statements)

References 39 publications

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“…We have shown that, with the same mean flow stresses (the static flow component), FPI, reflecting the dynamic component of flow mechanical stresses, determines distal PA cell responses. [86][87][88] We showed that, compared to low-pulsatility flow (LPF; FPI ¼ 0.2-0.5), HPF (FPI > 1) induced proinflammatory responses in the vascular endothelium. As illustrated in Figure 3, by imposing flows with varied FPIs on a monolayer of microvascular bovine PAECs, HPF with a physiological mean flow WSS (10-14 dyne/cm 2 ) consistently enhanced distal PAEC expression of proinflammatory molecules at the gene and protein levels, leading to in- Figure 3.…”

Section: Effects Of Large-pa Stiffening On Flow Pulsatility In the Pumentioning

confidence: 99%

Vascular Stiffening in Pulmonary Hypertension: Cause or Consequence? (2013 Grover Conference Series)

et al. 2014

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Recent studies have indicated that systemic arterial stiffening is a precursor to hypertension and that hypertension, in turn, can perpetuate arterial stiffening. Pulmonary artery (PA) stiffening is also well documented to occur in pulmonary hypertension (PH), and there is evidence that pulmonary vascular stiffness (PVS) may be a better predictor of outcome than pulmonary vascular resistance (PVR). We have hypothesized that the decreased flow-damping function of elastic PAs in PH likely initiates and/or perpetuates dysfunction of pulmonary microvasculature. Recent studies have shown that large-vessel stiffening increases flow pulsatility in the distal pulmonary vasculature, leading to endothelial dysfunction within a proinflammatory, vasoconstricting, and profibrogenic environment. The intricate role of stiffening-stimulated high pulsatile flow in endothelial cell dysfunction includes stepwise molecular events underlying PA hypertrophy, inflammation, endothelial-mesenchymal transition, and fibrosis. In addition to contributing to microenvironmental alterations of the distal vasculature, disordered proximal-distal PA coupling likely also plays a role in increasing ventricular afterload, ultimately causing right ventricle (RV) dysfunction and death. Current therapeutic treatments do not provide a realistic approach to destiffening arteries and, thus, to potentially abrogating the effects of high pulsatile flow on the distal pulmonary vasculature or the increased work imposed by stiffening on the RV. Scrutinizing the effect of PA stiffening on high pulsatile flow-induced cellular and molecular changes, and vice versa, might lead to important new therapeutic options that abrogate PA remodeling and PH development. With a clear understanding that PA stiffening may contribute to the progression of PH to an irreversible state by contributing to chronic microvascular damage in lungs, future studies should be aimed first at defining the underlying mechanisms leading to PA stiffening and then at improved treatment approaches based on these findings.Keywords: pulmonary hypertension, arterial stiffening, wave reflection, smooth muscle cell, endothelial cell, inflammation, right ventricle, treatment. Arterial stiffening is increasingly recognized as a risk factor of cardiovascular events as well as a guide for pharmacological treatment of cardiovascular diseases. Yet its exact role in the development and progression of cardiovascular diseases such as hypertension remains elusive. A recent study, however, presented convincing data supporting the possibility of a cause-effect relationship between arterial stiffness and systemic hypertension: higher levels of arterial stiffness and central pressures preceded and were associated with an increased risk of hypertension, but hypertension did not cause arterial stiffness. 1This work demonstrated that increased vascular stiffness could be a precursor to hypertension. A key implication from these observations is that arterial stiffness, when used as a measure of cardiovascula...

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Section: Effects Of Large-pa Stiffening On Flow Pulsatility In the Pumentioning

confidence: 99%

Vascular Stiffening in Pulmonary Hypertension: Cause or Consequence? (2013 Grover Conference Series)

et al. 2014

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“…16 An elevated resistance in the distal arteries causes a pressure increase in the large proximal vasculature, leading to proximal arterial remodeling in the form of increased arterial stiffness and thickness. This compromises the proximal vasculature's role as a hydraulic damper to the distal vessels, 17,18 causing distal endothelial cells to be exposed to nonphysiological pulse pressure and initiating a destructive cycle. Proximal arterial stiffening is also believed to affect wave reflections and has been shown to contribute to cardiac workload in the systemic circulation.…”

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confidence: 99%

The Role of Wall Shear Stress in the Assessment of Right Ventricle Hydraulic Workload

et al. 2015

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Pulmonary hypertension (PH) is a devastating disease affecting approximately 15-50 people per million, with a higher incidence in women. PH mortality is mostly attributed to right ventricle (RV) failure, which results from RV hypotrophy due to an overburdened hydraulic workload. The objective of this study is to correlate wall shear stress (WSS) with hemodynamic metrics that are generally accepted as clinical indicators of RV workload and are well correlated with disease outcome. Retrospective right heart catheterization data for 20 PH patients were analyzed to derive pulmonary vascular resistance (PVR), arterial compliance (C), and an index of wave reflections (Γ). Patient-specific contrast-enhanced computed tomography chest images were used to reconstruct the individual pulmonary arterial trees up to the seventh generation. Computational fluid dynamics analyses simulating blood flow at peak systole were conducted for each vascular model to calculate WSS distributions on the endothelial surface of the pulmonary arteries. WSS was found to be decreased proportionally with elevated PVR and reduced C. Spatially averaged WSS (SAWSS) was positively correlated with PVR (R 2 ¼ 0.66), C (R 2 ¼ 0.73), and Γ (R 2 ¼ 0.5) and also showed promising preliminary correlations with RV geometric characteristics. Evaluating WSS at random cross sections in the proximal vasculature (main, right, and left pulmonary arteries), the type of data that can be acquired from phase-contrast magnetic resonance imaging, did not reveal the same correlations. In conclusion, we found that WSS has the potential to be a viable and clinically useful noninvasive metric of PH disease progression and RV health. Future work should be focused on evaluating whether SAWSS has prognostic value in the management of PH and whether it can be used as a rapid reactivity assessment tool, which would aid in selection of appropriate therapies.

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“…These designs have had considerable use for screening inputs to numerical models, especially in the medical and biological sciences [100,116]. In these designs, each variable takes two levels and there are n = 2d + 2 runs.…”

Section: Systematic Fractional Replicate Designsmentioning

confidence: 99%

Design of Experiments for Screening

Woods

Lewis

2017

Handbook of Uncertainty Quantification

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The aim of this paper is to review methods of designing screening experiments, ranging from designs originally developed for physical experiments to those especially tailored to experiments on numerical models. The strengths and weaknesses of the various designs for screening variables in numerical models are discussed. First, classes of factorial designs for experiments to estimate main effects and interactions through a linear statistical model are described, specifically regular and nonregular fractional factorial designs, supersaturated designs and systematic fractional replicate designs. Generic issues of aliasing, bias and cancellation of factorial effects are discussed. Second, group screening experiments are considered including factorial group screening and sequential bifurcation. Third, random sampling plans are discussed including Latin hypercube sampling and sampling plans to estimate elementary effects. Fourth, a variety of modelling methods commonly employed with screening designs are briefly described. Finally, a novel study demonstrates six screening methods on two frequently-used exemplars, and their performances are compared.

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A new flow co-culture system for studying mechanobiology effects of pulse flow waves

Cited by 22 publications

References 39 publications

Vascular Stiffening in Pulmonary Hypertension: Cause or Consequence? (2013 Grover Conference Series)

Vascular Stiffening in Pulmonary Hypertension: Cause or Consequence? (2013 Grover Conference Series)

The Role of Wall Shear Stress in the Assessment of Right Ventricle Hydraulic Workload

Design of Experiments for Screening

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