Bioengineered Stromal Cell-Derived Factor-1α Analogue Delivered as an Angiogenic Therapy Significantly Restores Viscoelastic Material Properties of Infarcted Cardiac Muscle

摘要: Heart disease is the leading cause of death worldwide, with coronary heart causing one every six deaths in United States [1]. Following a myocardial infarction (MI), scar tissue gradually replaces myocardium that lost through process collagen deposition and an increase tensile strength [2]. Borderzone becomes hypocontractile, to left ventricular dilation, increased ventricle (LV) wall stress, decrease ejection fraction [3]. LV dilation perpetuates infarct expansion, adverse remodeling, dysfunction, which ultimately leads failure. The deleterious remodeling after MI causes significant change its geometry, resulting less efficient cardiomyocyte contraction finally, decline cardiac pump efficiency [4,5]. Understanding effect therapy on passive mechanical properties key component understanding efficacy. Angiogenesis mechanism by can be limited. It has previously been shown bone marrow-derived endothelial progenitor cells migrate toward ischemic incorporate into foci neovascularization [6]. We formerly demonstrated efficacy native protein, stromal cell-derived factor-1α (SDF), providing effective neovasculogenic for cardiomyopathy [7]. Subsequently, we developed ESA, computationally designed analog SDF-1α, intramyocardial injection enhances function promoting angiogenesis retention extracellular matrix (ECM) [8]. borderzone reduces deposition, limits spreading, thereby preserves healthy tissue. differential content modulus [9]. There interest among both clinical basic science communities regional stresses heart. free thick-walled complex fibrous structure, mainly consisting myocyte fibers. functional structural complexity poses challenge application biaxial biomechanical analysis state. Myocardium anisotropic fiber cross-fiber directions, exhibits nonlinear elasticity viscoelasticity, strain-rate dependence. structure also varies throughout LV, direction degree anisotropy dependent location from biopsy was taken. Computing require constitutive mathematical models active states [10]. In this study, sought validate experimental model testing combines viscoelastic reported elastic properties, order better understand how ESA treatment alters mechanics focus borderzone. Given our previous results [8,9], hypothesized infarcted muscle would improve ventricle, further evidence effects at level, addition globally preserving function.