Example 6: Model approach for cardiovascular diseases

Problem: to assess risk of clot formation resulted from NSAIDs administration.

Drugs assessed: aspirin, celecoxib, diclofenac, naproxen, indomethacin, ibuprofen, vioxx, etc. 

Motivation:

  • NSAIDs – popular drugs for pain relief and antipyretic, more recently started to be used in cancer and even depression.
  • Main target – COX1,2.
  • Wide range of adverse effects.
  • Selective COX-2 inhibitors (Coxibs) - efficient in pain relief but increase risk of clot formation.
  • Ability of platelets to form a clot can be characterized by Ca2+ concentration inside the platelets.

Approach:

  • to understand mechanisms of clot formation of existing NSAIDs we suggest to develop models of platelet, endothelial cell and blood circulation system
  • to apply these models to assess risk of clot formation under action of diffrent NSAIDs (aspirin, celecoxib, diclofenac, naproxen, indomethacin, ibuprofen, vioxx, etc).
ex6_cardio_1.jpg Result 1: Model of platelet has been developed and verified against data available internally and in public sources. As model of blood circulation system we have used advisory sowtware package Circulator.
ex6_cardio_2.jpg Result 2: Using the models of the platelets, endothelium cells and blood circulation system we have Ca2+ concentration inside the platelets at different parts of organism. This allowed us to assess the risk of clot formation resulted from different NSAIDs administration.
ex6_cardio_3.jpg Result 3: Computer modeling approach to assess risk of clot formation resulted from NSAIDs administration has been developed.

Pdf-description:

ISBSPb_cardiovascular_flyer.pdf (190.63 Kb)

 

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