COMBINED EXPERIMENTAL AND MATHEMATICAL MODELING OF MACROPHAGE DRIVEN LEFT VENTRICLE REMODELING POST MI
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. Ml 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 Ml. 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 at collagen I and Sppl (osteopontin; all p<0.05). In the plasma, matrix metalloprotcinase-9, tissue inhibitor of metalloprotcinase-1, and Sppl (osteopontin) levels increased post-MI (all p<0.05). Data analysis illustrated those changes in expression of matrix mctalloproteinase-9 (MMP-9), tissue inhibitor of mctalloproteinase-1 (TIMP-1), 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.
Modeling estimation left ventricular post myocardial infarction
YUFANG JIN JAMIE BERGER G.PATRICIA ESCOBAR QIUXIA DAI MERRY L.LINDSEY
Department of Electrical and Computer Engineering, University of Texas at San Antonio, San Antonio, Department of Medicine, University of Texas Health Science Center at San Antonio
国际会议
2008 International Conference on Machine Learning and Cybernetics(2008机器学习与控制论国际会议)
昆明
英文
4012-4017
2008-07-12（万方平台首次上网日期，不代表论文的发表时间）