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.
Heart valve disease causes significant illness and death in the United States, particularly in patients suffering from lupus, rheumatoid arthritis, and endocarditis, an inflammation of the heart. The researchers say that adjusting endothelial-derived microparticles during these and other diseases may become a means to prevent endothelial injury in valvular disease and perhaps other forms of heart disease.
Studies are now being conducted at the Children's Research Institute and the Medical College of Wisconsin to move toward such clinical applications. For example, Dr. John Densmore and colleagues have applied these in vitro (laboratory studies of tissue cells) to an in vivo, animal model of acute lung injury.
Preliminary data suggest that endothelial-derived microparticles play a role in worsening the injury through inhibition of vasodilation. Dr. Sander's co-authors for the Experimental Biology 2006 presentation include Dr. Klinkner, Dr. Densmore, Sushma Kaul, LeAnne Noll, Dr. Kirkwood A. Pritchard, Jr., and Dr. Keith T. Oldham from the department of surgery, division of pediatric surgery, at the Children's Research Institute and the Medical College of Wisconsin, and Dr. Dorothee Weihrauch from the department of anesthesiology the Medical College of Wisconsin in Milwaukee.