Combined experimental and mathematical modeling of macrophage driven left ventricle remodeling post MI

Yufang Jin, Jamie Berger, G. Patricia Escobar, Qiuxla Dai, Merry L. Lindsey

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Biological complexity and limited quantitative measurements impose major challenges to standard engineering methodologies for modeling of biological pathways. A new approach is presented to describe the dynamics of the left ventricle (LV) remodeling process post myocardial infarction (MI) in terms of the experimental measurements. MI is a leading cause of congestive heart failure, and currently there is a lack of biomarkers to predict how the left ventricle (LV) will respond to injury. The objective of this study is to measure extracellular matrix (ECM) gene levels in the LV post-MI to identify candidate factors that are predictive of remodeling post MI. Left ventricle from unoperated control mice (n=6) and the remote and infarct regions from 7 day post-MI mice (n=7) were studied. Of the 84 genes evaluated, 51 were differentially expressed in the post-MI LV. Significantly up regulated genes included α1 collagen I and Sppl (osteopontin; all p<0.05). In the plasma, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and Sppl (osteopontin) levels increased post-MI (all p<0.05). Data analysis illustrated those changes in expression of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-I), osteopontin (Sppl), and collagen correlated with each other. Mathematical simulation further illustrated the interaction among these factors and transforming growth factor β (TGF-β). In conclusion, the 5 proteins identified may be useful macrophage-dependent biomarkers for predicting changes in LV remodeling post-MI. The novelty of this study lies in the combination of experimental results with mathematical model.

Original languageEnglish (US)
Title of host publicationProceedings of the 7th International Conference on Machine Learning and Cybernetics, ICMLC
Pages4012-4017
Number of pages6
DOIs
StatePublished - 2008
Event7th International Conference on Machine Learning and Cybernetics, ICMLC - Kunming, China
Duration: Jul 12 2008Jul 15 2008

Publication series

NameProceedings of the 7th International Conference on Machine Learning and Cybernetics, ICMLC
Volume7

Other

Other7th International Conference on Machine Learning and Cybernetics, ICMLC
CountryChina
CityKunming
Period7/12/087/15/08

Keywords

  • Estimation
  • Left ventricular
  • Modeling
  • Post myocardial infarction

ASJC Scopus subject areas

  • Artificial Intelligence
  • Human-Computer Interaction
  • Control and Systems Engineering

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