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Veterinary Medicine

Cardiac research shows diseased heart valves in dogs produce serotonin

July 20, 2009

A significant part of the question of what causes mitral valve disease in dogs, giving scientists and medical experts clues into new possible ways to treat or prevent the disease, may have been solved by a Colorado State University veterinarian. The discovery refutes the current believe that mitral valve disease, the top heart disease in dogs, is inevitable as a part of aging in pets.

Dr. Chris Orton, a cardiac surgeon at Colorado State's Veterinary Teaching Hospital, has been investigating the role of serotonin in heart valve disease in dogs. It has been known for some time that drugs that enhance serotonin production in humans -- such as appetite suppressants, migraine medications and antidepressants -- cause drug-induced heart valve disease.

It turns out that naturally occurring heart valve disease, known as degenerative myxomatous heart valve disease, is virtually identical in dogs and humans. Dr. Orton's group has discovered that cells in diseased heart valves of both dogs and humans produce serotonin locally, and this may be driving the disease process.

Serotonin linked to heart malfunction

"Serotonin is made in the brain and in cells in the gut. We previously thought that those were the only places it was made before it is circulated in the blood," Orton said. "But we found the local creation of serotonin in diseased heart valves. We think that drug-induced and naturally occurring heart valve disease share the same mechanism for creating the disease - the production of serotonin. The valve is making serotonin, which causes its own disease. Serotonin is directly linked to pathologic changes in the valve, which cause the malfunction of the mitral valve."

Orton's group is working to discover what triggers the enzyme in the valve that makes serotonin, and he would like to launch a clinical trial on dogs to look at the impact of a drug that inhibits the enzyme that produces serotonin in the heart.

Mitral valve disease impacts the mitral valve, one of two valves on the left side of the heart. In degenerative valve disease, the valve becomes deformed and begins to leak. Serotonin is made in the gut by an enzyme called TPH1, Serotonin then goes into the blood stream where it is picked up by platelets which are involved in blood clotting. Orton's group has shown that TPH1 is present in high levels in abnormal mitral valves from both dogs and humans.

Trying to understand mechanism in cells that triggers the disease

"Like all diseases, mitral valve disease is mediated by cells," Orton said. "If we can understand the mechanism in cells that triggers the disease, we can slow, treat or prevent the disease process in new ways."

Mitral valve disease, also often called mitral valve prolapse in humans, tends to impact smaller breed dogs and usually develops when they are middle aged or older. Chihuahua, King Charles spaniels, and other toy and small breeds of dog tend to develop the disease more often than other breeds.
 
Of the dogs that develop heart disease, 40 percent develop mitral valve disease, and the disease is the eventual cause of about 70 percent of all heart failure in dogs.

Project CARE

Orton heads up Project CARE at Colorado State. The project focuses on researching the causes of and development of new treatments for mitral valve disease in dogs. The project is supported through grass roots funding. 


Contact: Dell Rae Moellenberg
E-mail: DellRae.Moellenberg@colostate.edu
Phone: (970) 491-6009