Pro-Inflammatory and Immunological Profile of Dogs with Myxomatous Mitral Valve Disease

SIMPLE SUMMARY: Myxomatous mitral valve disease (MMVD) is the most commonly acquired cardiac disease in dogs and is responsible for congestive heart failure. In this research, some inflammatory, immunological, and echocardiographic parameters were evaluated in dogs affected by MMVD in order to assess the involvement of additional pathophysiological mechanisms during the disease. The main results revealed that inflammation parameters increased according to the severity of the disease and suggested that inflammatory activation may play an important role in cardiac remodeling associated with the progressive volumetric overload in MMVD. Also, a relative increase in Treg cells was detected, suggesting that they could represent a regulatory mechanism for limiting the inflammatory immune response. ABSTRACT: Myxomatous mitral valve disease (MMVD) is a very frequently acquired cardiac disease in dog breeds and is responsible for congestive heart failure (CHF). The involvement of the immune system and pro-inflammatory cytokines in dogs with CHF due to mitral valve disease has not yet been extensively investigated. Here, we investigate the role of pro-inflammatory cytokines and the dysfunction of the immune system in dogs with different stages of severity through the blood assessment of CD4(+)FoxP3(+)regulatory T cells (Treg) cells, leptin, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 pro-inflammatory cytokines, and immunological and echocardiographic parameters. A total of 36 cardiopathic dogs, 14 females and 22 males, with MMVD were included. Mean age and body weight (BW) at the time of enrollment were 10.7 ± 2.77 years and 10.9 ± 6.69 kg, respectively. For the comparison of the pro-inflammatory and immunological parameters, two groups of healthy dogs were also established. Control group 1 consisted of young animals (n. 11; 6 females and 5 males), whose age and mean weight were 4.1 ± 0.82 years and 13.8 ± 4.30 kg, respectively. Control group 2 consisted of elderly dogs (n. 12; 6 females and 6 males), whose age and BW were 9.6 ± 0.98 years and 14.8 ± 6.15 kg, respectively. Of particular interest, an increase in Treg cells was observed in the cohort of MMVD dogs, as compared to the healthy dogs, as Treg cells are involved in the maintenance of peripheral tolerance, and they are involved in etiopathogenetic and pathophysiological mechanisms in the dog. On the other hand, TNF-α, IL-1β, and IL-6 significantly increased according to the severity of the disease in MMVD dogs. Furthermore, the positive correlation between IL-6 and the left ventricle diastolic volume suggests that inflammatory activation may be involved in cardiac remodeling associated with the progressive volumetric overload in MMVD.