PSIX-5 Changes in abundance of potential genes involved in cardiac disease progression in dogs with moderate and severe heart murmurs.

Abstract Myxomatous mitral valve disease is the most commonly diagnosed cardiovascular disease in dogs and is usually identified by the presence of a heart murmur caused by valvular regurgitation. As the disease progresses, blood volume overload of the left side of the heart can lead to cardiac remodeling through abnormal hypertrophy and eventually congestive heart failure. Therefore, the objective of this retrospective study was to investigate the relationship between heart murmur severity and changes in mRNA abundance as a potential indicator of disease progression. Blood samples for mRNA analysis were collected from 24 dogs at end of life, when quality of life had declined. All study procedures were approved by the Hill’s Institutional Animal Care and Use Committee. Blood samples were from dogs without heart murmurs (n=9; control), with moderate heart murmurs and not diagnosed with congestive heart failure (n=7; grades III/VI (n=4) and IV/VI (n=3)), and with severe heart murmurs (n=8; grades IV/VI (n=2), V/VI (n=5), and V-VI/VI (n=1)). Six of the dogs in the severe group were diagnosed with congestive heart failure including the two dogs diagnosed with grades IV/VI murmurs. Gene expression was determined using the NanoString nCounter® platform and data analysis was performed using the nSolver software provided by NanoString. In all dogs with heart murmurs, there was an increased (P< 0.05) abundance of granzyme A (2.02-fold), granzyme B (1.92-fold), granzyme H (1.60-fold), and adenosine receptor A3 (1.98-fold) when compared to control dogs without heart murmurs. Additionally, there was a decreased (P< 0.05) abundance of C-X-C motif chemokine ligand 8 (-2.11-fold), fibronectin 1 (-1.76-fold), and thioredoxin interacting protein (-1.54-fold) in dogs with murmurs compared to control dogs without murmurs. In the severe murmur group, there was an increased (P< 0.05) abundance of C-X-C motif chemokine ligand 8 (2.48-fold) and cathepsin G (1.62-fold) when compared to the moderate murmur group. These genes have been associated with cardiac remodeling, fibrosis and potentially other processes related to disease progression. As such, these identified genes may have the potential to be used as indicators of myxomatous mitral valve disease severity and progression. Additional validation and research of these identified genes is necessary to determine how nutritional support may affect their expression in dogs living with various stages of myxomatous mitral valve disease.