Adaptation of Endothelial Cells to Physiologically-Modeled, Variable Shear Stress

Uzarski, Joseph S.; Scott, Edward W.; McFetridge, Peter S.
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
Endothelial cell (EC) function is mediated by variable hemodynamic shear stress patterns at the vascular wall, where complex shear stress profiles directly correlate with blood flow conditions that vary temporally based on metabolic demand. The interactions of these more complex and variable shear fields with EC have not been represented in hemodynamic flow models. We hypothesized that EC exposed to pulsatile shear stress that changes in magnitude and duration, modeled directly from real-time physiological variations in heart rate, would elicit phenotypic changes as relevant to their critical roles in thrombosis, hemostasis, and inflammation. Here we designed a physiological flow (PF) model based on short-term temporal changes in blood flow observed in vivo and compared it to static culture and steady flow (SF) at a fixed pulse frequency of 1.3 Hz. Results show significant changes in gene regulation as a function of temporally variable flow, indicating a reduced wound phenotype more representative of quiescence. EC cultured under PF exhibited significantly higher endothelial nitric oxide synthase (eNOS) activity (PF: 176.0±11.9 nmol/105 EC; SF: 115.0±12.5 nmol/105 EC, p = 0.002) and lower TNF-a-induced HL-60 leukocyte adhesion (PF: 37±6 HL-60 cells/mm2; SF: 111±18 HL-60/mm2, p = 0.003) than cells cultured under SF which is consistent with a more quiescent anti-inflammatory and anti-thrombotic phenotype. In vitro models have become increasingly adept at mimicking natural physiology and in doing so have clarified the importance of both chemical and physical cues that drive cell function. These data illustrate that the variability in metabolic demand and subsequent changes in perfusion resulting in constantly variable shear stress plays a key role in EC function that has not previously been described.


Related Articles

  • Cytokines and endothelial adhesion molecules (sVCAM-1) in preeclampsia. Trunov, Aleksandr; Obukhova, Olga; Gorbenko, Olga; Shvayk, Alya; Trunova, Lilia // Advances in Bioscience & Biotechnology;Mar2013, Vol. 4 Issue 3, p352 

    In the purpose of studing the pathogenetic features of the pathological process there were investigated cytokine levels with proinflammatory and anti-inflammatory activity, and also the indicators of endothelial dysfunction in blood serum women with moderate and severe preeclampsia. There were...

  • Reconstituted High-Density Lipoprotein Modulates Activation of Human Leukocytes. Spirig, Rolf; Schaub, Alexander; Kropf, Alain; Miescher, Sylvia; Spycher, Martin O.; Rieben, Robert // PLoS ONE;Aug2013, Vol. 8 Issue 8, p1 

    An anti-inflammatory effect of reconstituted High Density Lipoprotein (rHDL) has been demonstrated in atherosclerosis and in sepsis models. An increase of adhesion molecules as well as tissue factor expression on endothelial cells in response to inflammatory or danger signals are attenuated by...

  • Anti-Inflammatory Effects of Concentrated Ethanol Extracts of Edelweiss (Leontopodium alpinum Cass.) Callus Cultures towards Human Keratinocytes and Endothelial Cells. Daniela, Lulli; Alla, Potapovich; Maurelli, Riccardo; Elena, Dellambra; Giovanna, Pressi; Vladimir, Kostyuk; Roberto, Dal Toso; Chiara, De Luca; Saveria, Pastore; Liudmila, Korkina // Mediators of Inflammation;2012, Vol. 2012, p1 

    Edelweiss (Leontopodium alpinum Cass.) is traditionally employed in folk medicine as an anti-inflammatory remedy. In nature, the plant is sparsely available and protected; therefore production of callus cultures was established. A concentrated ethanolic extract of culture homogenate, with...

  • Nanoliposomal Nitroglycerin Exerts Potent Anti-Inflammatory Effects. Ardekani, Soroush; Scott, Harry A.; Eum, Shane; Yang, Xiao; Ghosh, Kaustabh; Gupta, Sharad; Mohideen, Umar; Brunelle, Alexander R.; Wilson, Sean M. // Scientific Reports;11/20/2015, p16258 

    Nitroglycerin (NTG) markedly enhances nitric oxide (NO) bioavailability. However, its ability to mimic the anti-inflammatory properties of NO remains unknown. Here, we examined whether NTG can suppress endothelial cell (EC) activation during inflammation and developed NTG nanoformulation to...

  • Embedding Synthetic Microvascular Networks in Poly(Lactic Acid) Substrates with Rounded Cross-Sections for Cell Culture Applications. Huang, Jen-Huang; Kim, Jeongyun; Ding, Yufang; Jayaraman, Arul; Ugaz, Victor M. // PLoS ONE;Sep2013, Vol. 8 Issue 9, p1 

    Synthetic microvascular networks are essential to enable in vitro studies of cell biology, biophysics, hemodynamics, and drug discovery, as well as in applications involving tissue engineering and artificial vasculature. But current limitations make it challenging to construct networks...

  • Amniotic membrane: from structure and functions to clinical applications. Mamede, A.; Carvalho, M.; Abrantes, A.; Laranjo, M.; Maia, C.; Botelho, M. // Cell & Tissue Research;Aug2012, Vol. 349 Issue 2, p447 

    Amniotic membrane (AM) or amnion is a thin membrane on the inner side of the fetal placenta; it completely surrounds the embryo and delimits the amniotic cavity, which is filled by amniotic liquid. In recent years, the structure and function of the amnion have been investigated, particularly the...

  • Extracellular Vesicles: Evolving Factors in Stem Cell Biology. Nawaz, Muhammad; Fatima, Farah; Vallabhaneni, Krishna C.; Penfornis, Patrice; Valadi, Hadi; Ekström, Karin; Kholia, Sharad; Whitt, Jason D.; Fernandes, Joseph D.; Pochampally, Radhika; Squire, Jeremy A.; Camussi, Giovanni // Stem Cells International;11/16/2015, p1 

    Stem cells are proposed to continuously secrete trophic factors that potentially serve as mediators of autocrine and paracrine activities, associated with reprogramming of the tumor microenvironment, tissue regeneration, and repair. Hitherto, significant efforts have been made to understand the...

  • Anti-inflammatory Effects of Oleanolic Acid on LPS-Induced Inflammation In Vitro and In Vivo. Lee, Wonhwa; Yang, Eun-Ju; Ku, Sae-Kwang; Song, Kyung-Sik; Bae, Jong-Sup // Inflammation;Feb2013, Vol. 36 Issue 1, p94 

    Oleanolic acid (OA) is a triterpenoid known for its anti-inflammatory and anti-cancer properties; however, the anti-inflammatory effects of OA on lipopolysaccharide (LPS)-mediated pro-inflammatory responses have not been studied. Here, we first investigated the possible anti-inflammatory effects...

  • Anti-Inflammatory Properties of Sirtuin 6 in Human Umbilical Vein Endothelial Cells. Lappas, Martha // Mediators of Inflammation;2012, Vol. 2012, p1 

    A prominent feature of inflammatory diseases is endothelial dysfunction. Factors associated with endothelial dysfunction include proinflammatory cytokines, adhesion molecules, and matrix degrading enzymes. At the transcriptional level, they are regulated by the histone deacetylase sirtuin (SIRT)...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics