Project Summary Heart failure is a major growing public health problem with high morbidity and mortality. Despite extensive research and advances in drug development, there is still a strong demand for novel pharmacological agents that attenuate or reverse cardiac remodeling and prevent heart failure. Inflammatory mechanisms including macrophage activation and tissue fibrosis have been proposed to play an important role in cardiac remodeling and progression of heart failure. Interstitial fibrosis of viable myocardium following cardiac injury or pressure overload impairs tissue structure and behavior. Cells that are contributing to fibrosis of myocardium are primarily fibroblast and myofibroblats, which are phenotypically transformed fibroblast-like cells. Galectin-3 (a small protein) is emerging as a key player with a substantial role in the process of heart failure. It has been speculated that Galectin-3 promotes heart failure through involvement of multiple mechanisms including cardiac fibroblast proliferation, collagen deposition, and development of fibrosis. Excess collagen can potentially disturb extracellular matrix environment (ECM) resulting in alteration of spatial configuration of cardiac muscle fibers with respect to adjacent muscle elements. Alteration of muscle fiber configuration perturbs the cardiac clockwise and anticlockwise torsion, which is essential for normal pump function. Moreover, increase in myocardial collagen content could alter ventricular filling properties particularly by increasing diastolic stiffness. Clearly, an accurate assessment of left ventricular structure and function is an essential step to evaluate role of Galectin-3 inhibition in attenuating/reversing cardiac remodeling. In this study, sophisticated mathematical tools will be applied to in-vivo and ex-vivo cardiac images to identify correlation between Galectin-3 deletion and cardiac remodeling using two common murine models of heart failure (myocardial infarction and transverse aortic constriction). Immunohistochemistry techniques will be also used to evaluate Galectin-3 expression, presence of inflammatory cells (macrophages, fibroblasts and myofibroblasts), and tissue fibrosis in myocardial tissues. Outcome of this study provides novel mechanistic information that can guide the development of next generation therapeutic drugs targeting post-infarction and post-stress inflammatory response.