Martin Alexander Schwartz
talks with ScienceWatch.com and answers a few
questions about this month's Fast Moving Front in the field
of Clinical Medicine.
Article: A mechanosensory complex that mediates the
endothelial cell response to fluid shear
Authors: Tzima, E;Irani-Tehrani, M;Kiosses, WB;Dejana,
E;Schultz, DA;Engelhardt, B;Cao, GY;DeLisser,
Journal: NATURE, 437 (7057): 426-431 SEP 15 2005
Addresses: Scripps Res Inst, Dept Cell Biol, 10550 N Torrey
Pines Rd, La Jolla, CA 92037 USA.
Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037
Univ Milan, Mario Negri Inst Pharmacol Res, I-20139 Milan,
Univ Milan, Fac Sci, Dept Biomol & Biotechnol Sci, FIRC
Inst Mol Oncol, I-20139 Milan, Italy.
(addresses have been truncated)
Why do you think your paper is highly cited?
Does it describe a new discovery, methodology, or synthesis of
It provides the first coherent model for how forces from flowing blood are
transduced into a biochemical signal. What is particularly significant is
that it connects many effects of flow from previous studies into a single
pathway. It is both a new discovery as well as a synthesis of knowledge.
Would you summarize the significance of your paper
in layman's terms?
"Atherosclerosis is a chronic
inflammation of specific sites in artery
walls. Cholesterol and other risk factors
determine how atherosclerosis
Atherosclerosis is a chronic inflammation of specific sites in artery
walls. Cholesterol and other risk factors determine how atherosclerosis
progresses. However, the forces that flowing blood exert on the endothelial
cells that line our arteries are responsible for initiating
atherosclerosis. This paper describes a group of proteins that mediate the
response to flow in the endothelial cells. These inflammatory responses
initiate the event that leads to atherosclerosis.
How did you become involved in this research and
were any particular problems encountered along the way?
We got interested in the general area of how endothelial cells respond to
flow from a collaborator, Dr. Shu Chien of the University of San Diego,
Department of Bioengineering, who needed our expertise in integrin
signaling. Studying the integrins led us to the discovery of the
mechanotransduction complex that was reported in the Nature paper.
It was really just matter of following the data, one step at a time.
Where do you see your research leading in the
We would like to understand the basic molecular mechanisms of how forces
from blood act on the mechanotransduction complex. We are also exploring
the roles of integrin signals as possible avenues for pharmacological or
other interventions that could be used in the clinic.
Do you foresee any social or political implications
for your research?
I can foresee medical implications, but not social or political.
Martin Alexander Schwartz, Ph.D.
Professor of Microbiology, Biomedical Engineering, and Cell Biology
Mellon Urological Cancer Research Institute
Cardiovascular Research Center
University of Virginia
Charlottesville VA, USA