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July 15, 1999
Mechanical Forces Found To Exert Larger Role in Blood Vessel Health and Disease

University Park, Pa. --- Cholesterol, dietary fat, drugs and other chemical bio-regulators may get most of the media attention, but Penn State engineers have shown that mechanical forces, including shear stress, stretch and pressure, can play unsuspected but equivalent roles in some aspects of cardiovascular health and disease.

Dr. John Tarbell, distinguished professor of chemical engineering, and associates in Penn State's Biomolecular Transport Dynamics Laboratory, recently showed that there is a one-to-one correspondence between certain effects of shear stress, the frictional force exerted by blood flow, and a growth factor that stimulates the production of new blood vessels.

The Penn State group compared the effects of shear stress with that of vascular endothelial growth factor (VEGF) in laboratory tests with both human and bovine blood vessel tissue. VEGF is multifunctional and, in addition to promoting the growth of new blood vessels, it affects the ability of the cells on the interior surface of blood vessels, the endothelium, to allow fluid to pass through to the cells beneath.

The researchers showed that shear stress and VEGF not only cause similar changes in endothelium transport properties but also do so by the same chemical signaling pathways. Each of the tissue types the group investigated produces nitric oxide in response to shear stress, and nitric oxide is believed to be a key intermediate in the cell signaling cascade for both shear stress and VEGF, according to their recent paper.

Tarbell, who directs Penn State's Biomolecular Transport Dynamics Option for graduate study in the Life Sciences Consortium, notes that his group also investigates the effects of fluid flow as it passes across blood vessel walls. This transmural flow is six orders of magnitude or a million times slower than blood flow and amounts to a "seepage" through the wall's tissue matrix.

Nevertheless, even though the flow is slow, Tarbell and his associates have shown that it exerts shear stress that affects vessel function. For example, they have found that shear stress from transmural fluid flow stimulates the contraction of smooth muscle cells, which lie deep within the vessel wall. This may, in turn, contribute to the overall vessel contraction in response to an increase in blood pressure.

To estimate the shear stress levels on smooth muscle cells, the group used a computer simulation often used to model the flow of oil through sandstone. In future studies they hope to assess the relevance of the computational findings on live animals in addition to the cell culture systems they are currently studying.

Certain effects of fluid flows on smooth muscle cells become especially important when these cells are exposed directly to blood flow, for example, during angioplasty, vascular grafting or other surgical interventions, Tarbell notes.

In their recent laboratory studies with rat tissue, the Penn State group found that shear stress affects the contraction, growth and biochemical production rates of these smooth muscle cells in cell culture models which simulate both intact blood vessel walls and injured vessels where the cells are exposed directly to blood flow. Their results also suggest that exposed smooth muscle cells may take over certain endothelial cell functions when they experience shear stress from blood flow.

Tarbell and his research group recently reported these findings in two papers at the Summer Bioengineering Conference in Big Sky, Montana, June 16-20. The papers are: "Shear Stress and Vascular Endothelial Growth Factor (VEGF) Affect Endothelial Transport Properties through Common Signaling Pathways" by S. Lakshminarayanan, graduate student in chemical engineering, Y. Chang, graduate student in physiology, M. Hillsley, postdoctoral fellow, Thomas W. Gardner, associate professor of ophthalmology, and Tarbell; and "Effects of Flow on Vascular Smooth Muscle Cells" by S. Wang, postdoctoral fellow, R. Sharma, graduate student in bioengineering, S. Tarda, visiting scientist, Department of Mechanical Engineering and Science, Tokyo Institute of Technology, and Tarbell.

The research was supported in part by grants from the National Institutes of Health.


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