CARDIOVASCULAR PROTEOMICS AND MITRAL VALVE DISEASE IN DOGS: SEARCHING FOR A SEROLOGICAL BIOMARKER

CARDIOVASCULAR PROTEOMICS AND MITRAL VALVE DISEASE IN DOGS: SEARCHING FOR A SEROLOGICAL BIOMARKER Myxomatous valve disease (MVD) is the most common heart valvular disease in humans in Europe and United States, and it’s the primary naturally occurring heart disease in dogs. MVD is pathologically identical in humans and dogs, suggesting a common pathogenesis in these species, and creating an increasing interest in the canine MVD as a model for the human medicine. Nowadays, MVD is one of the most studied CVDs, because of its high prevalence in the clinical practice. Thanks to the research efforts, great diagnostic and therapeutic progresses have been made in the last decades, and continuous improvement are in the making. In recent years, new technologies have been used by the cardiovascular medicine, and the advancement of proteomic techniques has improved the methods available for investigating CVDs. Proteomics is the large-scale study of proteins and its application to uncover the protein function and structure in normal or disease states in the cardiovascular field is called cardiovascular proteomics. Even if the use of cardiovascular biomarkers is widespread in both human and veterinary medicine, the application of cardiovascular proteomics to the MVD study has recently begun. In the present study we selected a cohort of private-owned dogs recruited from the Cardiologic Service of the Department of Veterinary Science and Public Health. The dogs were selected with precise inclusion and exclusion criteria. Two breeds were considered: Cirneco dell’Etna and Cavalier King Charles Spaniels. The Cirneco dell’Etna breed is a poorly diffuse Italian hunting breed whose CVDs prevalence has never been studied before, while the Cavalier King Charles Spaniel breed is the most studied breed for all the MVD researches, because of the high prevalence of MVD, the early onset and the strong scientifically proved hereditary component. The objective of the present study was to search one or more than one serological biomarkers in dogs affected by MVD, comparing blood samples from the healthy dogs of the groups with blood samples from the dogs affected by different stages of MVD. The proteomics results were then matched with the clinical and echocardiographic data obtained in the clinical trial of all the patients included in the study, to find a connection available in the clinical practice. 64% of the Cirneco dell’Etna dogs included in the study were affected by MVD, and all the dogs older than 6 years had echocardiographic signs of MVD. The proteomic analysis of the Cirneco samples gave the following results: the alpha-1-antytripsina (A1AT) was up-regulated in the patients affected by MVD, according to the severity of the pathology, while the complement C3 was down-regulated with the development of MVD, according to the stage of the disease. Among the Cavalier King Charles breed there was a high prevalence of MVD (63%) and a very low medium age of onset (4 years). The proteomic analysis of the Cavalier King Charles Spaniel samples produced the following results: the serum albumin was down-regulated, according to the severity of the pathology, while it was observed a strong up-regulation of some specific types of IgG and IgM, according to the severity of the pathology. Based on our study results, the Cirneco dell’Etna breed is a primitive hunting breed predisposed to the development of MVD, with an early onset of the pathology. All the CdE dogs older than 6 years should be therefore evaluated for MVD, and included in a screening program. We confirmed that Cavalier King Charles Spaniel is a breed with a high prevalence of MVD and an early onset too, as previously reported. The proteomic analysis conducted on our samples and correlated to the clinical results, indicate that the MVD is a pathology that is strictly connected to a chronic inflammation state. The up-regulation of A1AT, IgG, IgM, and the down-regulation of complement C3 and serum albumin are connected with an inflammatory status, that cause a depletion of the components of the complement system, an activation of the acute phase proteins and of the components of immunity response like IgG and IgM immunoglobulins. The hypothesis that MVD could be related to a chronic inflammation was already speculated in the last years, and, based on the present study results, we think that the analysis of the inflammatory mediators in MVD patients could be a great chance to uncover the pathogenic mechanism at the base of mitral valve disease.