01529-A: Platelet, myocardial, and valvular serotonin concentrations in healthy dogs and dogs with mitral valve disease

Grant Status: Closed

Grant Amount: $10,305
Mark A. Oyama, DVM; University of Pennsylvania
December 1, 2010 - November 30, 2012

Sponsor(s): Labrador Retriever Club, Newfoundland Club of America Charitable Trust, Rottweiler Health Foundation

Breed(s): Cavalier King Charles Spaniel, Norfolk Terrier
Research Program Area: Cardiology
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Project Summary

In humans, increased serotonin (5-HT) signaling causes valvular disease with pathologic characteristics that are very similar to canine mitral valve disease (MVD). We have previously shown that serum 5HT concentrations are elevated in dogs with MVD as well as in dogs that are at high risk for development of disease. Our findings specifically identified the Cavalier King Charles Spaniel (CKCS) as a breed of dog with elevated 5HT. These findings as well as from others in the veterinary field advance a hypothesis that 5HT signaling is an important component of MVD in dogs. The most likely source of elevated serum 5HT is platelets, such that platelets are thought to contain 99% of all circulating 5HT. It has been recently shown that platelet contents can activate disease changes within the heart muscle of experimental animals. The platelet, heart muscle, and valve-specific content of 5HT in dogs with heart disease has not been previously reported. Thus, we wish to specifically determine if platelet 5HT is the source of elevated serum 5HT in dogs with spontaneous disease as well as to quantify the amount of 5HT in both the left ventricular muscle and mitral valve leaflets of affected dogs. By doing so, we will further our hypothesis that 5HT stimulation is an important aspect of DMVD in dogs. Results of this study demonstrated that a vast majority of circulating 5HT is contained in platelets. Healthy CKCS had higher platelet 5HT concentrations than healthy non-CKCS breeds, and this could suggest and link between 5HT and the high predisposition of MMVD in the CKCS. Results also revealed that 5HT concentration in the left ventricular heart muscle as well as in the mitral valve leaflet itself was increased in dogs with MMVD. To our knowledge, this has not been previously reported. This finding further strengthens the hypothesis that 5HT within the MV leaflet plays a role in the progressive changes seen in MMVD. The data obtained from this study support future studies into the relationship of 5HT and MMVD, as well as stimulating interest in studies to evaluate 5HT-blocker drugs as potential therapy for MMVD.


Cremer, S. E., Singletary, G. E., Olsen, L. H., Wallace, K., Häggström, J., Ljungvall, I., … Oyama, M. A. (2014). Serotonin Concentrations in Platelets, Plasma, Mitral Valve Leaflet, and Left Ventricular Myocardial Tissue in Dogs with Myxomatous Mitral Valve Disease. Journal of Veterinary Internal Medicine, 28(5), 1534–1540. https://doi.org/10.1111/jvim.12420

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