2016 Benjamin Franklin Medal in Mechanical Engineering presented to Shu Chien, M.D., Ph.D.

摘要

The dynamics in blood circulation is determined by the functional states of its components, i.e., cardiac contractility, vascular hindrance, and blood viscosity. While blood viscosity is a determinant of blood flow, the shear stress resulting from blood flow also modulates blood viscosity. This shear dependence of blood viscosity is a result of the composition of the blood as a suspension of deformable and aggregable blood cells in protein-containing plasma. The interplay between blood rheology and shear stress has significant implications on circulatory regulation in health and in cardiovascular and hematological diseases. Shear stress also acts on the vascular endothelial cells (ECs) to modulate their gene and protein expressions to regulate vascular function in health and diseases, particularly those resulting from atherosclerosis such as myocardial infarction and stroke. Understanding of the mechanisms of mechanotransduction and gene regulation underlying the shear-modulation of vascular function is essential for the improvement of diagnosis, treatment, and prevention of these fatal diseases. Shu Chien has elucidated the fundamental determinants of blood viscosity, viz. cell concentration, plasma viscosity, and shear-dependent cell aggregation and cell deformability, which is determined in turn by intracellular viscosity, cell geometry, and membrane properties. He has applied such fundamental mechanical and molecular knowledge to the understanding of the role of blood rheology in cardiovascular and hematological diseases such as myocardial infarction, stroke, and sickle cell disease. His findings have led to improved management of these disorders such as the use of blood thinners to prevent restenosis after vascular stenting. By using a combination of cellular, molecular, and genomic techniques, coupled with innovative engineering experimentation and analysis, Dr. Chien has elucidated the roles of flow patterns in mechanotransduction and gene regulation in endothelial cells, including mechano-sensing, molecular signaling, genetic and epigenetic modulation, and functional regulation in response to mechanical forces. He formulated the concept that the adaptive response of intracellular rheology to different shear stress patterns is a key mechanism for homeostasis. He established the principle that shear stress with a clear direction is athero-protective, while that without is atherogenic; this has led to the recognition of the importance of minimizing disturbed flow in the treatment and prevention of a variety of clinical conditions.