How does endothelial damage contribute to disease progression in canine myxomatous mitral valve disease? A prospective longitudinal study

Myxomatous mitral valve disease (MMVD) is the most common cause of heart disease in adult dogs, affecting millions worldwide. MMVD typically progresses slowly, over several years, eventually resulting in heart failure in approximately half of affected dogs. Narrowing of the blood vessels (arteriosclerosis) is a common post mortem finding in dogs with MMVD, which leads to the development of heart muscle scarring (fibrosis), due to the compromised blood supply. This scar tissue compromises heart muscle function and so contributes to worsening heart disease. One possible explanation for the development of arteriosclerosis is damage to the endothelial cells that line the entire cardiovascular system.

We have developed new methods to study endothelial damage in canine blood and tissue and will investigate whether this is associated with arteriosclerosis, myocardial fibrosis and disease severity in dogs with MMVD.

Aims & Objectives
1. To characterise endothelial damage in dogs with different stages of MMVD
2. To visualise the endothelium in canine cardiac tissue and to assess relationship between endothelial damage and myocardial arteriosclerosis and fibrosis
3. To validate circulating markers of endothelial damage in canine blood and investigate their relationships with disease severity
4. To investigate changes in markers of endothelial damage over time and their relationships with disease progression in a cohort of dogs with MMVD of varying severity

Methods
Clinical studies – longitudinal evaluation of MMVD in dogs by serial echocardiography
Tissue studies – immunohistochemistry and electron microscopy
Circulating biomarkers of endothelial damage – validation of ELISAs, etc.