Cardiac tissue constructs for biophysical testing and drug-screening
时间:12月27日下午4:00
地点:医学科学楼B323
报告人:Elliot L. Elson, Ph. D.
(Alumni Endowed Professor, Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine)
报告摘要:
Hypertension kills 1 in every 5000 Americans each year and affects the majority of those over the age of 55. Following prolonged hypertension, cardiac fibroblasts within the heart convert to myofibroblasts, a larger, contractile phenotype that produces fibrous connective tissue and thereby stiffens heart muscle, impairing its function. Furthermore, after a myocardial infarction (heart attack), heart muscle cells die in a localized region of the heart that has been deprived of its blood supply. These muscle cells are replaced by myofibrobasts that form an “infarct scar” that is also stiff relative to normal heart muscle. In addition to these mechanical effects, myofibroblasts disrupt normal patterns of electrical excitation of cardiomyoctyes, potentially leading to cardiac failure due to perturbation of the normal heart rhythm. Therapies that control myofibroblasts would evidently be of value, but little is known about their mechanical and electrophysiological interactions with cardiomyocytes. We therefore developed and analyzed a model engineered heart tissue (EHT) system that allows us to dissect how myofibroblasts, cardiomyocytes, and the extracellular matrix interact to modulate the functioning of myocardium. Results suggest that mild fibrosis is beneficial to contractile function of EHTs, but that this benefit is lost as myofibroblasts persist and proliferate. Results further support the idea of using these model tissues to search for drugs that ameliorate the effects of fibrosis. This talk will summarize results suggesting mechanisms by which myofibroblasts alter the contractile response of myocardium and present some initial thoughts on treatments to improve this response by cytoskeletal regulation.
报告人简况:
Elliot Elson, Ph.D., studies dynamics and equilibrium of interactions of molecules in cells and model systems. Prof. Elson serves as the Alumni Endowed Professor of Biochemistry and Molecular Biophysics at the Washington University School of Medicine, and is a fellow of the Biophysical Society and of the American Academy of Arts and Sciences.