April 21, 2003
When a person suffers a heart attack or stroke, it is usually because there is some damage to the lining cells of an artery that has been affected by coronary artery disease.
HOUSTON, TX - Understanding mechanisms that trigger platelets to form blood clots is critical to the development of new drugs to treat heart attacks, strokes and peripheral vascular diseases.
"Within the circulatory system, there is a delicate balance between factors that promote blood clots and factors that prevent clots," said Michael H. Kroll, M.D., a staff physician at the Houston Veterans Affairs Medical Center (HVAMC).
"We want to understand these molecular interactions, so that medications can be designed that will treat dangerous clotting but not impact the normal mechanisms of clotting that keep wounds from bleeding."
An abnormality in the blood, blood vessel or blood flow can result in the formation of a blood clot. Blood clots cause problems when they form in, or move into, the coronary arteries, the carotid arteries of the neck, or the large arteries of the leg. Arterial clots consist of platelets that stick together and then form a clump which blocks blood flow.
A heart attack occurs when the blood supply to part of the heart muscle itself, the myocardium, is severely reduced or stopped. The reduction or stoppage happens when one or more of the coronary arteries supplying blood to the heart muscle are blocked.
Kroll, who is also an associate professor of medicine, molecular physiology, and biophysics at Baylor College of Medicine, is studying specific proteins involved in the platelet clotting that occurs in diseased blood vessels. The research utilizes human platelets from healthy individuals and genetically-engineered hamster cells.
"We use actual human platelets in machines that mimic specific blood flow conditions that only develop in the diseased arteries. This allows us to study the molecules that may be specific switches, turned on only in the setting of a heart attack or stroke," he said.
Kroll's group then uses genetically-engineered cells to focus experiments on the specific molecular switches that his group and others have discovered during investigations using intact human platelets.
When a person suffers a heart attack or stroke it is usually because there is some damage to the lining cells of an artery that has been affected by coronary artery disease. The damage to the artery lining, called the endothelium, causes underlying arterial tissues to be exposed to blood.
Kroll and other medical researchers at the HVAMC, Baylor College of Medicine, and Rice University are studying a platelet surface receptor called glycoprotein Ib. This receptor attaches to the protein, von Willebrand factor, found in the blood and in the tissue beneath the artery lining.
When an artery is injured, abnormal blood flow causes von Willebrand factor to attach to platelet glycoprotein Ib. This attachment anchors platelets to the damaged vessel wall and switches the platelets "on." When platelets are switched on, they play a critical role in blood clot formation.
By determining how blood flow, von Willebrand factor, and glycoprotein Ib influence platelet stickiness and clumping, researchers hope to identify unique molecular inter-actions that impact clotting in diseased blood vessels.
"Our group has already identified a specific interaction that we believe could be a target for inhibiting clot formation. If further research confirms this, we would have the opportunity to work on drug development," Kroll said.
In addition to heart disease and stroke, their research utilizing platelets may one day impact treatments for leukemia and hemophilia.
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Point of Contact: VHAHOU Public Affairs04/21/04 08:25