Under normal physiological conditions, low levels of microparticles are continually being shed into the blood from the endothelium - the cells that line the inside of blood vessels and some organs -and appear to cause no problems. But during some diseases, the level of endothelium-derived microparticles circulating in the blood rises.
Now, researchers from the Medical College of Wisconsin in Milwaukee and Children's Research Institute report the first evidence that elevated levels of these microparticles can lead to disease and dysfunction of the heart valves.
Dr. Tara Sander presented the study results at Experimental Biology 2006 in San Francisco. Dr. Denise Klinkner, a surgical research fellow in Dr. Tara Sander's laboratory, conducted the study as part of ongoing research in Dr. Sander's laboratory to understand if abnormally high levels of endothelium-derived microparticles negatively affect the endothelial cells lining the heart valve leaflets, cells that are essential for normal function and repair and that often are injured or become dysfunctional in valve disease.
Dr. Sander's presentation was part of the scientific program of the American Society for Investigative Pathology. In the study, endothelial cells from the mitral valve tissue of a heart of an infant who received a heart transplant were exposed to increasing levels of endothelial-derived microparticles. At lower levels, comparable to those in nondisease states, the particles stimulated growth of the mitral valve endothelial cells, which is good. But at higher levels, equivalent to those seen in disease, the same particles inhibited the growth of these same cells. They also interfered with the cells' ability to respond to growth factors, indicating a disruption of normal pathways that control growth and migration of endothelial cells.
Interestingly, endothelial cells from other parts of the body responded differently to the different levels of microparticles. For example, while high levels comparable to disease states inhibited the growth of endothelial cells from mitral valve tissue, these same levels stimulate growth of endothelial cells from umbilical veins. Data from this study will appear in an upcoming issue of the journal Shock.