PSXI-3 Decreased Circulating Concentrations of CD21 and CD19 in Canines with Heart Murmur and Associated Valvular Cardiovascular Disorder

Abstract

Abstract Myxomatous mitral valve disease (MMVD) is a commonly diagnosed canine heart disease characterized by a thickening of the mitral valve. While it affects dogs of all genetic backgrounds, the breeds most commonly affected include small to medium dogs. The underlying causes of MMVD are not clear but pathological changes include alterations in the extracellular matrix and collagen, and activation of matrix metalloproteinases (MMPs), leading to subsequent myocardial remodeling. Inflammatory signaling pathways are hypothesized to influence the progression of the valve lesion contributing to valvular regurgitation. One of the clinical characteristics of MMVD in dogs is heart murmur. We assessed the circulating concentrations of inflammatory markers in dogs that were clinically diagnosed by a veterinarian as having MMVD with at least grade 4 heart murmur. RNA was extracted from blood samples collected in PAXgene tubes from dogs with heart murmurs (n=6; 4 dogs had grade 5/6 and 2 dogs had 4/6 heart murmur; 9.3-15.11 yr) and control dogs (n=6; 9.4-15.10 yr) with no history of cardiovascular problems. Gene expression was assessed using NanoString nCounter and analysis performed using Nanostring’s nSolver software. There was a significant decrease in the concentrations of CD21 (-1.88 fold) and CD19 (-1.84 fold) in MMVD compared with controls (both p< 0.05). CD21 and CD19 are parts of CD21/CD19/CD81 complex that act as a co-receptor to the B cell receptor. A decrease in CD19 and CD21 indicates a possible disruption in the homeostasis of B-cell activation and may contribute to chronic inflammation. In addition, pro-inflammatory cytokines/chemokines and receptors that were increased in MMVD include CCL5 (1.74), Lymphotoxin β (1.49), Interferon-γ (1.35), CCL3 (1.28), CCL4 (1.28), IL-18R1 (1.27) and MMP-9 (1.27, all NS). Our results indicate the importance of targeting the B-lymphocyte-associated signaling pathway and selected cytokines for restoring immune homeostasis and reducing inflammation in MMVD.