Following myocardial infarction, the mechanical properties of the healing scar are a critical determinant of left ventricular function, infarct expansion, aneurysm formation and rupture, and ventricular remodeling. Until recently, the only therapeutic options for addressing these consequences were pharmacologic. However, in the past few years, the introduction of a range of options for modifying the cardiac mechanical environment has fundamentally altered our options for clinical postinfarction therapy. The dynamic in vivo cardiac mechanical environment is now just as valid a potential therapeutic target as hormone receptors or signaling cascades. In principle, if mechanical signals that govern scar healing, infarct expansion, aneurysm formation, or ventricular remodeling can be identified, they can be modified. Therefore, one major goal of our work on mechanics of healing infarcts is to provide a better understanding of the evolution of scar structure and mechanics as a platform for designing and appropriately applying therapies to improve ventricular function and to prevent infarct expansion, aneurysm formation, and adverse left ventricular remodeling. Considerable evidence also suggests that the interaction between healing infarcts and the surrounding myocardium works in the other direction: mechanical stimuli applied to the infarct by the myocardium can direct the development of infarct structure and mechanical properties. In particular, our work under the initial funding period of this project (12/01/03 - 11/30/07) revealed a striking correlation between scar structural and mechanical anisotropy in different animal models and the deformation patterns experienced by healing infarcts in those models. We hypothesize that mechanical environment governs the development of anisotropy in healing infarcts and represents a potentially important therapeutic target for directing infarct healing to optimize ventricular function and help prevent long-term adverse remodeling. The work proposed here will test this hypothesis using a combination of unique in vitro model systems and a new innovative approach to manipulating the mechanical environment of healing myocardial infarcts in vivo.
The goal of this research is to understand the structure and mechanical properties of the scar tissue that forms following a heart attack. The mechanical properties of this scar tissue are important in determining heart function during the weeks to years following a heart attack.
| Haggart, Charles R; Ames, Elizabeth G; Lee, Jae K et al. (2014) Effects of stretch and shortening on gene expression in intact myocardium. Physiol Genomics 46:57-65 |
| Rouillard, Andrew D; Holmes, Jeffrey W (2014) Mechanical boundary conditions bias fibroblast invasion in a collagen-fibrin wound model. Biophys J 106:932-43 |
| Ames, E G; Lawson, M J; Mackey, A J et al. (2013) Sequencing of mRNA identifies re-expression of fetal splice variants in cardiac hypertrophy. J Mol Cell Cardiol 62:99-107 |
| Fomovsky, Gregory M; Clark, Samantha A; Parker, Katherine M et al. (2012) Anisotropic reinforcement of acute anteroapical infarcts improves pump function. Circ Heart Fail 5:515-22 |
| Chandran, Preethi L; Paik, David C; Holmes, Jeffrey W (2012) Structural mechanism for alteration of collagen gel mechanics by glutaraldehyde crosslinking. Connect Tissue Res 53:285-97 |
| Ateshian, Gerard A; Morrison 3rd, Barclay; Holmes, Jeffrey W et al. (2012) Mechanics of Cell Growth. Mech Res Commun 42:118-125 |
| Fomovsky, Gregory M; Rouillard, Andrew D; Holmes, Jeffrey W (2012) Regional mechanics determine collagen fiber structure in healing myocardial infarcts. J Mol Cell Cardiol 52:1083-90 |
| Rouillard, Andrew D; Holmes, Jeffrey W (2012) Mechanical regulation of fibroblast migration and collagen remodelling in healing myocardial infarcts. J Physiol 590:4585-602 |
| Fomovsky, Gregory M; Macadangdang, Jesse R; Ailawadi, Gorav et al. (2011) Model-based design of mechanical therapies for myocardial infarction. J Cardiovasc Transl Res 4:82-91 |
| Fomovsky, Gregory M; Holmes, Jeffrey W (2010) Evolution of scar structure, mechanics, and ventricular function after myocardial infarction in the rat. Am J Physiol Heart Circ Physiol 298:H221-8 |
Showing the most recent 10 out of 18 publications
