A Fluid-Structure Interaction Index of Coronary Plaque Rupture

Ilegbusi, Olusegun J.; Valaski-Tuema, Eric

doi:10.1007/978-3-642-11615-5_11

Cited by 3 publications

(4 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The upregulation of PI16 by KLF2 would suggest it plays an athero-protective role in the endothelium, by limiting proteolysis of the sub-endothelial matrix. This would help resist the increased mechanical forces to which the endothelium is exposed, especially overlying stenotic plaques, where the level of shear stress can exceed 300 dynes/cm 2 5711121314. Cigarette use is a risk factor for endothelial erosion33 and is known to increase the circulating levels of inflammatory cytokines, including TNFα34.…”

Section: Discussionmentioning

confidence: 99%

“…By contrast, normal laminar shear stress (LSS) (10–15 dynes/cm 2 in the coronary circulation)4567 induces EC quiescence, resistance to inflammation (by inducing a myriad of anti-inflammatory genes and repressing pro-inflammatory gene expression) and stimulates the release of anti-coagulative and anti-thombolytic mediators, all of which are atheroprotective8910. In advanced atherosclerosis, ECs overlying stenotic atherosclerotic plaques are exposed to elevated shear stress (ESS), potentially exceeding 300 dynes/cm 2 5711121314. However, the effects of ESS on ECs is less well studied.…”

mentioning

confidence: 99%

See 1 more Smart Citation

PI16 is a shear stress and inflammation-regulated inhibitor of MMP2

Hazell

Peachey

Teasdale

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Raised endothelial shear stress is protective against atherosclerosis but such protection may be lost at sites of inflammation. We found that four splice variants of the peptidase inhibitor 16 (PI16) mRNA are among the most highly shear stress regulated transcripts in human coronary artery endothelial cells (HCAECs), in vitro but that expression is reduced by inflammatory mediators TNFα and IL-1β. Immunohistochemistry demonstrated that PI16 is expressed in human coronary endothelium and in a subset of neointimal cells and medial smooth muscle cells. Adenovirus-mediated PI16 overexpression inhibits HCAEC migration and secreted matrix metalloproteinase (MMP) activity. Moreover, PI16 inhibits MMP2 in part by binding an exposed peptide loop above the active site. Our results imply that, at high endothelial shear stress, PI16 contributes to inhibition of protease activity; protection that can be reversed during inflammation.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

PI16 is a shear stress and inflammation-regulated inhibitor of MMP2

Hazell

Peachey

Teasdale

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The time-averaged wall shear stress in human coronary arteries has been measured as approximately 16 dynes/cm 2 by a number of studies (Stone et al, 2003 ; Wentzel et al, 2003 ; Joshi et al, 2004 ; Gijsen et al, 2008 ), with 12–15 dynes/cm 2 being most frequently used to simulate normal arterial shear stress in vitro. In contrast, the wall shear stress overlying human plaques, has been measured at 50–>300 dynes/cm 2 , depending on the degree of stenosis (Stone et al, 2003 ; Gijsen et al, 2008 ; Torii et al, 2009 ; Ilegbusi and Valaski-Tuema, 2010 ; Leach et al, 2010 ; Teng et al, 2010 ). However very little is known about the response of endothelial cells to laminar shear stress elevated above normal physiological levels; the maximum in vitro shear stress applied to human endothelial cells was reported by the Moraweitz group (Duerrschmidt et al, 2006 ), who studied the effects of up to 50 dynes/cm 2 on the production of ROS and the expression of NOX2 and p47 subunits of NADPH oxidase.…”

mentioning

confidence: 99%

Characterization of the differential response of endothelial cells exposed to normal and elevated laminar shear stress

White

Hayes

Lehoux

et al. 2011

Journal Cellular Physiology

106

View full text Add to dashboard Cite

Most acute coronary events occur in the upstream region of stenotic atherosclerotic plaques that experience laminar shear stress (LSS) elevated above normal physiological levels. Many studies have described the atheroprotective effect on endothelial behavior of normal physiological LSS (approximately 15 dynes/cm2) compared to static or oscillatory shear stress (OSS), but it is unknown whether the levels of elevated shear stress imposed by a stenotic plaque would preserve, enhance or reverse this effect. Therefore we used transcriptomics and related functional analyses to compare human endothelial cells exposed to laminar shear stress of 15 (LSS15-normal) or 75 dynes/cm2 (LSS75-elevated). LSS75 upregulated expression of 145 and downregulated expression of 158 genes more than twofold relative to LSS15. Modulation of the metallothioneins (MT1-G, -M, -X) and NADPH oxidase subunits (NOX2, NOX4, NOX5, and p67phox) accompanied suppression of reactive oxygen species production at LSS75. Shear induced changes in dual specificity phosphatases (DUSPs 1, 5, 8, and 16 increasing and DUSPs 6 and 23 decreasing) were observed as well as reduced ERK1/2 but increased p38 MAP kinase phosphorylation. Amongst vasoactive substances, endothelin-1 expression decreased whereas vasoactive intestinal peptide (VIP) and prostacyclin expression increased, despite which intracellular cAMP levels were reduced. Promoter analysis by rVISTA identified a significant over representation of ATF and Nrf2 transcription factor binding sites in genes upregulated by LSS75 compared to LSS15. In summary, LSS75 induced a specific change in behavior, modifying gene expression, reducing ROS levels, altering MAP kinase signaling and reducing cAMP levels, opening multiple avenues for future study. J. Cell. Physiol. 226: 2841–2848, 2011. © 2011 Wiley-Liss, Inc.

show abstract

“…To incorporate the anisotropic tissue elasticity, a multizone-based geometric representation is employed. While multizone representations have been previously investigated for arterial blood flows [12], it has not been used for investigating airflow inside the lungs. The usage of such a geometric representation avoided errors in airflow analyses caused by airway segmentation errors and reduced the computation time as compared to the timings previously reported in [7].…”

Section: Introductionmentioning

confidence: 99%

Modeling Airflow Using Subject-Specific 4DCT-Based Deformable Volumetric Lung Models

Ilegbusi

Seyfi

et al. 2012

International Journal of Biomedical Imaging

View full text Add to dashboard Cite

Lung radiotherapy is greatly benefitted when the tumor motion caused by breathing can be modeled. The aim of this paper is to present the importance of using anisotropic and subject-specific tissue elasticity for simulating the airflow inside the lungs. A computational-fluid-dynamics (CFD) based approach is presented to simulate airflow inside a subject-specific deformable lung for modeling lung tumor motion and the motion of the surrounding tissues during radiotherapy. A flow-structure interaction technique is employed that simultaneously models airflow and lung deformation. The lung is modeled as a poroelastic medium with subject-specific anisotropic poroelastic properties on a geometry, which was reconstructed from four-dimensional computed tomography (4DCT) scan datasets of humans with lung cancer. The results include the 3D anisotropic lung deformation for known airflow pattern inside the lungs. The effects of anisotropy are also presented on both the spatiotemporal volumetric lung displacement and the regional lung hysteresis.

show abstract

A Fluid-Structure Interaction Index of Coronary Plaque Rupture

Cited by 3 publications

References 13 publications

PI16 is a shear stress and inflammation-regulated inhibitor of MMP2

PI16 is a shear stress and inflammation-regulated inhibitor of MMP2

Characterization of the differential response of endothelial cells exposed to normal and elevated laminar shear stress

Modeling Airflow Using Subject-Specific 4DCT-Based Deformable Volumetric Lung Models

Contact Info

Product

Resources

About