Endothelial Glycocalyx Damage in Dogs with Myxomatous Mitral Valve Disease
Myxomatous mitral valve disease (MMVD) is the most common cause of heart disease in adult dogs, affecting millions worldwide. Small- and medium-sized dogs, especially Cavalier King Charles Spaniels, Dachshunds, Poodles and Yorkshire terriers, are predisposed to MMVD. MMVD typically progresses slowly, over several years, eventually resulting in heart failure in approximately half of affected dogs.
The blood vessels in the body, including the heart, are protected by a gel-like layer (glycocalyx) which can be damaged by hormones released in response to heart disease. One of the outcomes of glycocalyx damage is narrowing of the blood vessels (arteriosclerosis). Arteriosclerosis results in decreased blood supply and injury to the heart muscle, which is repaired with scar tissue (fibrosis). This scar tissue compromises the ability of the heart muscle to contract and relax and so contributes to worsening heart disease.
To date it has been difficult to study the protective glycocalyx layer in dogs, but we have optimised novel methods to do so in canine blood and tissue and will, for the first time, investigate whether damage to the glycocalyx is associated with blood vessel narrowing, scarring of the heart muscle and disease severity in dogs with MMVD. The main goal of this study is to further characterize glycocalyx damage in dogs with MMVD and ultimately demonstrate glycocalyx damage as a potential novel therapeutic target in this extremely common disease.
Significance to Canine Health
Therapies addressing the underlying pathophysiology of MMVD are urgently needed. None are currently available, largely reflecting the lack of knowledge of the important pathophysiological mechanisms underpinning the disease. If endothelial glycocalyx (eGCX) damage contributes to severity of MMVD, therapies that repair the eGCX could improve the quality and quantity of life in millions of dogs worldwide. Sulodexide, a commercially-available compound consisting of heparan sulphate (80%) and dermatan sulphate (20%), has been shown to increase eGCX dimensions in human diabetic patients, suggesting therapeutic promise in conditions associated with eGCX damage.
Expected Outcomes, Significance, and Application of Findings
The primary aim of the study is to characterise eGCX damage in dogs with MMVD, thereby advancing our understanding of its role in the pathophysiology of this highly prevalent disease and suggesting novel therapeutic targets to improve patient outcome.
Furthermore, this project will utilize novel techniques developed in our laboratory to visualise eGCX damage and its circulating surrogate markers that will enable future study of its role in the pathophysiology of a wide range of canine disease processes, including sepsis, fluid therapy, diabetes, chronic kidney disease and the cardiorenal syndrome. This opens the possibility of improving the health and welfare of a significant proportion of the canine population worldwide.
The Langford Trust for Animal Health and Welfare is supporting this important work.
If you are interested in helping address heart disease in dogs, please if you can