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Configurator Based Integrated Dynamic Simulation of Reverse Cholesterol Transport (RCT)
Author(s) -
Adhikari Sam
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb543
Subject(s) - cholesterylester transfer protein , reverse cholesterol transport , abca1 , chemistry , cholesterol , computer science , computational biology , biochemistry , biology , transporter , gene , lipoprotein
Major constituents of RCT include acceptors such as high density lipo‐protien (HDL) and apoliproprotein A‐1 (ApoA‐1), and enzymes such as lechtin:cholesterol acyltransferase (LCAT), Phospholipid transfer protein (PLTP), hepatic lipase (HL), and cholesterol ester transfer protein (CETP). Realistic quantitative modeling of RCT is extremely difficult through conventional methods. It requires a software configurator aided, database driven systems biology platform. Our RCT quantitative model based dynamic, integrated simulation uses many complex models including kinetics to evaluate cholesterol efflux from the macrophages to ApoA‐1 via ABCA1 and ABCG1. The model is enhanced by the quantitative RCT effects of Caveolin, Sterol 27‐hydroxylase (CYP27A1), scavenger receptor SR‐B1 transport processes, and ABCG5/G8 hepatobiliary and intestinal sterol extraction gene. The net RCT pathway is quantified with multiple parameters that can change depending on clinical in‐vivo or in‐vitro conditions. A standard relational database model holds all the objects of the quantitative simulation model. An optimization algorithm matches the aggregate model with the clinical RCT datasets. It automatically adjusts all the parameters till it can find the best solution.