Serum Serotonin Concentration Is Associated with Severity of Myxomatous Mitral Valve Disease in Dogs

Abstract

Background: The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has recently been suggested to play a role in the development of naturally acquired myxomatous mitral valve disease (MMVD) in dogs.Aim: To investigate the association between serum 5-HT concentration and MMVD severity in dogs, and to assess potential associations between serum 5-HT concentrations and dog characteristics, echocardiographic variables, heart rate, systolic blood pressure, presence of macrothrombocytosis, and plateletcrit.Animals: A total of 120 client-owned dogs. Material and Methods: Dogs were prospectively recruited and were classified by standard echocardiography into healthy (dogs of breeds predisposed to MMVD, but without echocardiographic evidence of the disease), mild, moderate, or severe MMVD groups. Serum 5-HT concentrations were analyzed using an ELISA.Results: Dogs with severe MMVD had lower serum 5-HT concentrations than healthy dogs (P = .0025) and dogs with mild MMVD (P = .0011). Unilinear and multiple regression analyses showed that serum 5-HT concentrations decreased with increasing left atrial to aortic root ratio (LA/Ao), were higher in Cavalier King Charles Spaniel (CKCS) dogs compared to dogs of other breeds, and were higher in female dogs than in male dogs. The LA/Ao was the variable most strongly associated with serum 5-HT concentration.Conclusions and Clinical Importance: The finding of higher serum 5-HT concentrations in dogs of breeds predisposed to the early onset of MMVD (CKCS) and dogs with mild MMVD suggests that alterations in 5-HT signaling might play a role in progression of early stages of MMVD.

Serum serotonin concentration in lean and obese dogs with myxomatous mitral valve disease

“…A significant low 5-HT concentration was found between control and moderate to severe groups, although there were no differences between the control and mild group, and between the mild and the moderate to severe group. These findings are similar to the previous study that 5-HT concentration was decreasing with increasing MMVD severity and high 5-HT levels in early stages of MMVD are associated with the development of MMVD [8].…”

“…The result is similar to that of Ljungvall [8]. Also, dogs with moderate to severe MMVD had significantly lower serum 5-HT concentrations than the control group in the obese groups.…”

“…Recently, 5-HT has been suggested to have a role in the development of MMVD in dogs [8,9]. The mitral valve leaflets are naturally thin, translucent, thickening and elongation with disease progression, which can lead to MMVD in dogs [13].…”

Evaluation of chemokines CXCL8 and CCL2, serotonin, and vascular endothelial growth factor serum concentrations in healthy dogs from seven breeds with variable predisposition for canine idiopathic pulmonary fibrosis

“…Serum CXCL8, CCL2, and VEGF measurements were performed using commercial canine ELISA kits (R&D Systems) in duplicate, according to the manufacturer's instructions. Serum 5-HT measurement was performed using a commercial human ELISA kit (IBL international) previously validated in dogs (Ljungvall et al, 2013).…”

“…In humans, altered regulation of the serotonin pathway is thought to be associated with the development of pulmonary fibrosis since an increased expression of 5-HT receptors was found in IPF lungs (Fabre and Crestani, 2010;Konigshoff et al, 2010) and anti-serotonin therapy was shown to attenuate induced pulmonary fibrosis in mice (Konigshoff et al, 2010;Skurikhin et al, 2012). In dogs, 5-HT has essentially been studied in the pathogenesis of the DMVD, another fibrotic disease (Oyama and Levy, 2010;Ljungvall et al, 2013;Cremer et al, 2014;Mangklabruks and Surachetpong, 2014). Increased 5-HT blood concentrations were found in healthy KCS in comparison with healthy dogs from other breeds predisposed or not to DMVD (Arndt et al, 2009).…”