Researchers Track Complex Links in Blood Vessels’ Signaling System

As blood courses through the human body, blood vessels dilate and constrict according to pressures exerted in the bloodstream. Proteins called integrins play a crucial role in relaying signals that govern this process, and medical researchers at The Texas A&M University System Health Science Center are using innovative techniques to discover more about these proteins.
Gerald A. Meininger, Ph.D., of the Health Science Center’s College of Medicine, is the principal investigator of a research group just awarded a five-year, $1.4 million grant from the National Institutes of Health to study integrins’ role in regulating blood vessel diameter.
“The ability of integrins to affect blood vessel tone has broad implications,” Meininger said. “It helps to determine how a vessel’s diameter is regulated and how that regulation might be impaired during disease processes like hypertension and atherosclerosis or heart attacks, which lead to vascular remodeling — thickening and stiffening of blood vessel walls that make them prone to failure. Blood vessel diameter is very important in terms of controlling blood flow to tissues and regulating blood pressure.
“The common denominator is the sensitivity of blood vessel cells to changes in mechanical pressure, their response to physical and mechanical signals that lead to changes in diameter,” he observed. “These responses involve integrins as one link in sensor pathways which signal individual muscle cells in the vessel walls to shorten or lengthen, changing the size of the entire blood vessel.”
Integrins are protein receptors on the membrane surface of nearly all body cells, where they serve as the glue which attaches the cell to the protein scaffold surrounding cells and tissues, an extracellular matrix made up of a variety of proteins, the most familiar of which may be collagen. In 1996, Meininger’s research group discovered the role of one of the integrins in regulating blood vessel diameter. To date, the group has studied three of the proteins, but Meininger suspects there may be other integrins involves since as many as 24 varieties of integrins have been identified.
Researchers on the integrin project are using cells cultured in the laboratory from blood vessels that feed capillaries and that are smaller than a human hair.
“These vessels control blood pressure and flow and are known as resistance vessels because of their ability to dilate and constrict according to blood pressure and flow demands,” Meininger said. “In a unique approach to the field of vascular research, we?ve developed a hybrid microscopy to examine these cells, using a fluorescence light microscope and a relatively new tool called atomic force microscopy.”
Atomic force microscopy works much like an old-time phonograph. Similar to the record player?s needle skimming groves in vinyl records, the microscope works by passing a stylus over a cell’s surface, sensing changes in the elevation and composition of the material scanned and sending its data to a computer, which constructs an image of the cell being examined. The instrument is so sensitive that it can deliver and measure force at the cellular level in the range of picoNewtons, a minute amount of force.
Meininger is Regents Professor and Associate Head of the Department of Medical Physiology at the College of Medicine and Director of the Division of Vascular Biology of the Cardiovascular Research Institute. Other collaborators in the integrin project include George Davis, Ph.D., professor of Medical Pathology and Medicine; Michael Davis, Ph.D., professor of Physiology; and Jerome Trzeciakowski, Ph.D., professor of Pharmacology and Toxicology.
“The current grant will allow us to investigate how integrins sense mechanical force produced by blood pressure and blood flow,” Meininger said. “Our research will seek to understand how cells sense these things and generate a signal that initiates blood vessel response.”
The Texas A&M University System Health Science Center provides the state with health education, outreach and research. Its five components located in communities throughout Texas are Baylor College of Dentistry, the College of Medicine, the Graduate School of Biomedical Sciences, the Institute of Biosciences and Technology and the School of Rural Public Health.