%0 Journal Article
%T Combining experimental and mathematical modeling to reveal mechanisms of macrophage-dependent left ventricular remodeling
%A Yu-Fang Jin
%A Hai- Chao Han
%A Jamie Berger
%A Qiuxia Dai
%A Merry L Lindsey
%J BMC Systems Biology
%D 2011
%I BioMed Central
%R 10.1186/1752-0509-5-60
%X By examining the extracellular matrix (ECM) gene expression and plasma analyte levels in C57/BL6J mice LV post-MI and ECM gene responses to transforming growth factor (TGF-¦Â1) in cultured cardiac fibroblasts, we found that key factors in LV remodeling included macrophages, fibroblasts, transforming growth factor-¦Â1, matrix metalloproteinase-9 (MMP-9), and specific collagen subtypes. We established a mathematical model to study LV remodeling post-MI by quantifying the dynamic balance between ECM construction and destruction. The mathematical model incorporated the key factors and demonstrated that TGF-¦Â1 stimuli and MMP-9 interventions with different strengths and intervention times lead to different LV remodeling outcomes. The predictions of the mathematical model fell within the range of experimental measurements for these interventions, providing validation for the model.In conclusion, our results demonstrated that the balance between ECM synthesis and degradation, controlled by interactions of specific key factors, determines the LV remodeling outcomes. Our mathematical model, based on the balance between ECM construction and destruction, provides a useful tool for studying the regulatory mechanisms and for predicting LV remodeling outcomes.Myocardial infarction (MI) is a leading cause of congestive heart failure (CHF) [1,2]. In response to the MI stimulus, the left ventricle (LV) undergoes structural and functional adaptations that collectively have been termed as LV remodeling [3]. Adverse LV remodeling progresses to CHF in about 25% of post-MI patients, but the mechanisms that drive this progression remain poorly understood. During LV remodeling, both extracellular matrix (ECM) degradation and synthesis increase [4]. When ECM degradation dominates over synthesis, LV rupture can occur. When ECM synthesis dominates over degradation rates, fibrosis can occur. Fibrosis increases myocardial stiffness and further depresses LV function to culminate in CHF [5,6]. Ther
%U http://www.biomedcentral.com/1752-0509/5/60