A new drug discovery model for heart valves



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WASHINGTON, March 15, 2019 / PRNewswire / – An article published in Experimental Biology and Medicine (Volume 244, Number 3, February 2019) (https://journals.sagepub.com/doi/pdf/10.1177/1535370219829006) describes a new model of cardiac valve physiology. The study, led by Dr. Carla Lacerda, from the Department of Chemical Engineering to Texas Tech University in Lubbock, TX, USA, indicates that a cyclic radial stress of 10% on the isolated anterior leaflets of the mitral valve provides a true physiological environment that can be used for mechanistic studies and drug discovery.

Heart valves are responsible for maintaining a steady blood flow in one direction. It is estimated that more than 5 million Americans live with a heart valve that works poorly. Mechanical stress (tensile and shear forces) is a major cause of valve degeneration. Valve endothelial cells, one of two types of cells including heart valves, can protect valves from degeneration. Understanding the molecular mechanisms used by these cells to react to stress will provide new drug targets for the treatment of valvular disease.

In this study, Dr. Lacerda and colleagues used proteomic badysis to evaluate the effect of cyclic radial deformity at 10% on isolated heart valves. Extend negatively regulated cytoskeletal proteins and proteins involved in energy metabolism, suggesting a state of rest. The elimination of the endothelium resulted in a downregulation of the extracellular matrix and cell-matrix adhesion proteins, suggesting a protective role of the endothelium in the homeostasis of the extracellular matrix. The elimination of the endothelium is also a regulated activity of protein synthesis. Together, these studies provide new insights into the molecular mechanisms that regulate the response of heart valves to mechanical stress. These studies also define a true physiological environment that can be used to study valve function and discover new drugs to prevent, slow down or reverse valve disease. Dr. Lacerda stated that "the development of in vitro models to properly guide the design of replacement tissues is essential for the advancement of tissue engineering techniques." It is only by developing constructs imitating physiology, in which cells behave as they are in vivo, understand the molecular mechanisms used by cells to defend themselves from environmental aggression. "

Dr. Steven R. Goodman, Editor-in-chief of Experimental Biology and Medicine, Lacerda and colleagues provide proteomic and interactomic badysis of proteins and protein networks affected by mechanical stretching of the mitral valve and / or endothelial removal. This will be a useful platform for future studies on the pathophysiology of heart valves. "

Experimental Biology and Medicine is a global journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. The newspaper was created in 1903. Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn more about the benefits of being a member of society, visit www.sebm.org. If you want to publish in the newspaper, please visit http://ebm.sagepub.com.

SOURCE Experimental Biology and Medicine

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