Insights into Serotonin Signaling Mechanisms Associated with Canine Degenerative Mitral Valve Disease
Article first published online: 11 NOV 2009
Copyright © 2009 by the American College of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine
Volume 24, Issue 1, pages 27–36, January/February 2010
How to Cite
Oyama, M.A. and Levy, R.J. (2010), Insights into Serotonin Signaling Mechanisms Associated with Canine Degenerative Mitral Valve Disease. Journal of Veterinary Internal Medicine, 24: 27–36. doi: 10.1111/j.1939-1676.2009.0411.x
- Issue published online: 4 JAN 2010
- Article first published online: 11 NOV 2009
- Submitted July 15, 2009; Revised September 1, 2009; Accepted September 23, 2009.
- Cellular biochemistry;
- Molecular biology;
- Valvular disease
Little is known about the molecular abnormalities associated with canine degenerative mitral valve disease (DMVD). The pathology of DMVD involves the differentiation and activation of the normally quiescent mitral valvular interstitial cell (VIC) into a more active myofibroblast phenotype, which mediates many of the histological and molecular changes in affected the valve tissue. In both humans and experimental animal models, increased serotonin (5-hydroxytryptamine, 5HT) signaling can induce VIC differentiation and myxomatous valve damage. In canine DMVD, numerous lines of evidence suggest that 5HT and related molecules such as transforming growth factor-β play a critical role in the pathogenesis of this disease. A variety of investigative techniques, including gene expression, immunohistochemistry, protein blotting, and cell culture, shed light on the potential role of 5HT in the differentiation of VIC, elaboration of myxomatous extracellular matrix components, and activation of mitogen-activated protein kinase pathways. These studies help support a hypothesis that 5HT and its related pathways serve as an important stimulus in canine DMVD. This review describes the pathological characteristics of canine DMVD, the organization and role of the 5HT pathway in valve tissue, involvement of 5HT in human and experimental models of valve disease, avenues of evidence that suggest a role for 5HT in naturally occurring DMVD, and finally, a overarching hypothesis describing a potential role for 5HT in canine DMVD.