For the first time, researchers at the University of Pennsylvania Medical Center have confirmed that bone--similar to that found in the human skeleton--is present in a substantial portion of diseased heart valves. This finding, which sets the stage for more in-depth research on the biochemical process by which valves transform into bone, could lead to the development of therapies to prevent or treat heart-valve disease. The broader problem of valve calcification is the leading reason for heart-valve-replacement surgery. According to the American Heart Association, more than 71,000 Americans required the life-saving procedure in 1995.
This line of inquiry should also help scientists better understand how calcium deposits form in the arteries of patients with atherosclerosis and other vascular diseases. And, the information gleaned will be useful to researchers who are studying rare disorders--such as fibrodysplasia ossificans progressiva--where bone forms outside the skeleton.
"While the problem of valve calcification has been recognized for over 100 years, this is the first study to look at a large series of diseased heart valves and find bone," explains Emile R. Mohler, III, MD, director of vascular medicine at Penn. Mohler and his colleagues will present their findings at the annual meeting of the American College of Cardiology in Atlanta.
The team studied 228 valves removed from patients who underwent valve-replacement surgery from 1994 to 1997 at the Hospital of the University of Pennsylvania. Organized, hard-bone tissue--identical to that found in a living human skeleton--was found in 30 of the valves, which, according to Dr. Mohler, "was a higher percentage than we expected."
This work represents one important step in a long-term series of investigations to understand the biochemical pathways that govern the build-up of calcium, and now bone, in heart valves. In late 1997, Mohler and colleagues found osteopontin--a protein that makes up the molecular scaffolding to which calcium sticks in the formation of bone--in calcified valves. "Finding this protein and actual bone is evidence that valve calcification is an active process of laying down organized bone tissue, not a passive one, as was once thought," says Mohler.
But that still leaves the question: How did bone cells get into the heart? "One theory is that, under the right conditions, either valve cells or inflammatory cells at the area of heart damage undergo a genetic change and start making bone-cell proteins," suggests Mohler. "But, the most important question is: What's the trigger?"
The team's ultimate goal is to devise a treatment to prevent the hardening in the first place. Knowing how and why bone forms in the soft tissue of the heart might lead to a preventive or corrective therapy. The next steps are to develop cell and animal models of valve calcification.
Penn colleagues Francis H. Gannon, Carol Reynolds, and Frederick S. Kaplan also participated in this study.
Editor's Note: Dr. Mohler can be reached at 215-662-9016 until Friday March 28, after which time he will be at the ACC meeting. Please contact Karen Kreeger to reach Dr. Mohler in Atlanta.
The University of Pennsylvania Medical Center's sponsored research ranks third in the United States, based on grant support from the National Institutes of Health, the primary funder of biomedical research in the nation. In federal fiscal year 1997, the medical center received $175 million. News releases from the medical center are available to reporters by direct E-mail, fax, or U.S. mail, upon request. They are also posted to the center's website (http://www.med.upenn.edu) and EurekAlert! (http://www.eurekalert.org), a resource sponsored by the American Association for the Advancement of Science.
The above post is reprinted from materials provided by University Of Pennsylvania Medical Center. Note: Materials may be edited for content and length.
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