Modeling, analysis and simulation of left ventricular remodeling post myocardial infarction

Progressive remodeling of the left ventricle (LV) following myocardial infarction (MI) can lead to congestive heart failure (CHF), but the underlying initiation factors remain poorly defined. The objective of this study, accordingly, was to clarify the regulatory mechanisms of LV remodeling using integrated computational and experimental approaches. A novel mathematical model was developed to study LV remodeling post-MI by quantifying the dynamic balance between extracellular matrix (ECM) construction and destruction.

Experimental results of post-MI ECM gene and plasma concentration levels and cardiac showed that key factors in LV remodeling included macrophages, fibroblasts, transforming growth factor-beta (TGF-beta), matrix metalloproteinase-9 (MMP-9), and collagen elements. The mathematical model incorporated these key factors and demonstrated that TGF-beta stimuli and MMP-9 interventions with different strengths and interfering time lead to different LV remodeling responses. The predictions fell within the range of experimental measurements for these interventions, providing validation for the model. The established mathematical model is Lyapunov stable with the determined parameters.

In conclusion, the results demonstrate that the balance between ECM synthesis and degradation controlled by interactions of specific key factors determine net LV remodeling outcomes. The mathematical model based on the balance between ECM construction and destruction predicts remodeling outcomes and provides a useful tool to study post-MI regulatory mechanisms.