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

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.

Prognostic Efficacy of Complete Blood Count Indices for Assessing the Presence and the Progression of Myxomatous Mitral Valve Disease in Dogs

“…Moreover, contrary to previous research, which showed no significant difference in PLR between the healthy and MMVD groups [40], the present study found a significant increase in PLR in the MMVD group compared to that in the control group. These results are consistent with those of previous veterinary studies that found an increase in platelets and a decrease in lymphocytes in the MMVD group compared to healthy controls [2,27,41] and with previous human studies that confirmed the significance of PLR as a prognostic factor in patients with heart failure [29,38].…”

“…Myxomatous mitral valve disease (MMVD) is the most common cause of congestive heart failure (CHF) and the most common acquired cardiac disease in dogs, accounting for 75% of all heart disease cases [ 1 , 2 , 3 ]. Conventional echocardiography and cardiac biomarkers, such as N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI), are the gold standard methods for diagnosing CHF [ 1 ].…”

Differences in Levels of Mitochondrial DNA Content at Various Stages of Canine Myxomatous Mitral Valve Disease

“…Although our study did not encompass comprehensive data on specific inflammatory biomarkers, it is noteworthy that we observed a slight elevation in the white blood cell count in dogs afflicted by heart failure. This increase may be indicative of an inflammatory response activated by plasma mtDNA, a phenomenon paralleling observation in studies of chronic heart failure patients [34] and investigations involving dogs with MMVD [8,45,46]. These collective findings shed light on the intricate interplay between mtDNA and inflammation in the context of cardiac diseases.…”

Evaluation of antioxidant status and lipid peroxidation in dogs with myxomatous mitral valve degeneration stage B1

“…Oxidative stress, defined as “an imbalance between oxidants and antioxidants in favor of oxidants, resulting in impaired disruption of redox signaling and control and/or molecular damage” ( 6 ), has also been linked to cardiac remodeling and myocardial damage in humans ( 7 ). Oxidative stress is also associated with the inflammatory response of cardiac cells, which has already been confirmed in dogs with heart failure ( 8 , 9 ) and in dogs with different stages of MMVD ( 10 ).…”