• DocumentCode
    33561
  • Title

    CREPE: Mathematical Model for Crosstalking of Endothelial Cells and Hepatocyte Metabolism

  • Author

    Valvano, Giuseppe ; Orsi, Giorgio ; Guzzardi, Maria Angela ; Vozzi, F. ; Vozzi, Giovanni

  • Author_Institution
    Interdept. Res. Center E. Piaggio, Univ. of Pisa, Pisa, Italy
  • Volume
    61
  • Issue
    1
  • fYear
    2014
  • fDate
    Jan. 2014
  • Firstpage
    224
  • Lastpage
    230
  • Abstract
    The liver shows a close coexistence between endothelial cells and hepatocytes (HepG2). Endothelial cells´ main purpose is to protect (HepG2) from blood vessel shear stress, acting as a barrier, but experimental evidence suggests that they could also play a role in regulating (HepG2) glucose metabolism. A well-known singular effect in hepatocyte-endothelial co-cultures is the reduction of glucose consumption respect to (HepG2) in single culture. (HepG2) were shown to reduce their glucose consumption supporting energy needs of endothelial cells. Monti have studied the effects of endothelin-1 (Et-1) on Glucokinase activity in adult rat (HepG2). They observed a reduction in hepatocytes Glucokinase catalytic rate, which is dependent on Et-1 concentration. We developed crosstalking of endothelial cells and hepatocyte metabolism (CREPE) that is a mathematical model of the endothelin-1 mediated crosstalk between HepG2 and endothelial cells (human umbilical vein endothelial cells) in a traditional static co-culture system. CREPE was validated against experimental data, showing good agreement with them. CREPE can be a starting point to develop predictive tools on complex and highly interconnected environments.
  • Keywords
    biochemistry; blood vessels; catalysis; cellular biophysics; physiological models; sugar; CREPE mathematical model; HepG2; blood vessel shear stress; cell crosstalk; endothelin-1; glucose consumption; glucose metabolism; hepatocyte metabolism; hepatocyte-endothelial co-cultures; hepatocytes glucokinase catalytic rate; human umbilical vein endothelial cells; Biochemistry; Biological system modeling; Equations; Genetics; Mathematical model; Substrates; Sugar; Computational systems biology; cell crosstalk; endothelin-1 (Et-1); glucokinase; mathematical modeling;
  • fLanguage
    English
  • Journal_Title
    Biomedical Engineering, IEEE Transactions on
  • Publisher
    ieee
  • ISSN
    0018-9294
  • Type

    jour

  • DOI
    10.1109/TBME.2013.2272942
  • Filename
    6557437