Identification of matrix metalloproteinase-2 and -9 activities within the intestinal mucosa of dogs with chronic enteropathies

Abstract

BackgroundMatrix metalloproteinases (MMPs) 2 and 9 are zinc- and calcium-dependent endopeptidases involved in the breakdown and reconstitution of extracellular matrix under both physiological and pathological conditions. Mucosal MMP-2 and -9 activities have been reported to be upregulated in the intestine of humans with inflammatory bowel disease (IBD), and in animal models of IBD. However, their involvement in the pathogenesis of canine chronic enteropathies (CE) is unknown. This study investigated mucosal pro- and active MMP-2 and -9 activities in dogs with CE and healthy dogs using gelatin zymography, and also to determine the association of their activities in dogs with CE with the canine IBD activity index (CIBDAI), histopathologic findings, the clinical outcome, and hypoalbuminemia. Intestinal mucosal samples from duodenum, ileum, colon, and cecum were collected from 40 dogs with CE and 18 healthy Beagle dogs.ResultsIn dogs with CE, the number of samples positive for mucosal pro- and active MMP-2 was significantly higher in the duodenum (P < 0.0001 and P = 0.011, respectively), ileum (P = 0.002 and P = 0.018, respectively), and colon (P < 0.0001 and P = 0.002, respectively), compared with healthy controls. Mucosal pro-MMP-9-positive samples in the duodenum and colon were significantly more frequent in dogs with CE than in healthy dogs (P = 0.0004 and P = 0.001, respectively). Despite the presence of mucosal samples positive for active MMP-9 in the intestinal segments of dogs with CE, the difference compared to healthy controls did not reach statistical significance. None of the intestinal mucosal samples in healthy dogs showed gelatinolytic activity corresponding to the control bands of active MMP-2 and -9. Mucosal active MMP-9 activities displayed a significant positive association with the severity of neutrophil infiltration in the duodenum (P = 00.040), eosinophils in the cecum (P = 00.037), and the CIBDAI score for ileum samples (P = 0.023). There was no significant association of pro- and active MMP-2 and -9 levels with the clinical outcome or hypoalbuminemia.ConclusionsThis study is the first to demonstrate upregulation of mucosal pro- and active MMP-2 and pro-MMP-9 in the intestine of dogs with CE compared to healthy dogs. The results provide supporting evidence for the possible involvement of MMP-2 and -9 in the pathogenesis of canine CE.

Changes of inflammatory and oxidative stress biomarkers in dogs with different stages of heart failure

“…This would indicate that there is an inflammation associated with CHF specially in severe cases. Similar to our results, significantly higher serum CRP concentration was found in dogs with decompensated CHF compared with compensated dogs with heart disease and healthy dogs [ 13 ].…”

“…To the best of the authors’ knowledge, this is the first study that reports changes in a panel of inflammatory and oxidative stress biomarkers in dogs with different stages of heart failure (stage A, B2, C and D) and their correlations with echocardiographic findings. In this study, CHF due to MMVD or DCM was diagnosed based on a thorough cardiopulmonary assessment as reported in the previous studies [ 5 , 13 ], and classified by stage A through D according to the ACVIM consensus statement guidelines [ 3 ].…”

“…The present study is associated with several limitations. First, the sample size was small and dogs were not sub-divided as MMVD and DCM in this study, although this approach has been used in previous studies of changes in selected analytes in dogs with CHF [ 13 , 42 ]. Therefore, this should be considered a pilot study and additional studies should be continued with a large number of animals with the same disease (MMVD or DCM or other diseases that can produce CHF) in separate groups.…”

“…A transthoracic echocardiographic examination was performed as reported previously [ 13 , 51 , 52 ]. Briefly, cardiac measurements were done using conventional modalities (2-D, M-mode, and color Doppler) and imaging techniques (right parasternal short and long axis, left apical 4–5 chamber and subcostal views) with phased-array cardiac transducers in all dogs (Caris Plus Esaote, Italy).…”

“…Although both of them are commonly considered non-inflammatory conditions [ 6 , 7 ], studies have found increased circulating inflammatory cytokines in dogs and humans with CHF due to MMVD [ 8 , 9 ] and DCM [ 7 , 10 ]. Increased expression and release of inflammatory cytokines such as tumour necrosis factor (TNF-α), as well as serum C-reactive protein (CRP), have been described in humans [ 11 , 12 ] and dogs with CHF [ 13 ]. Increased levels of monocyte chemoattractant protein 1 (MCP-1) and decreased levels of interleukins have also been found in dogs with CHF [ 8 ], but there is no data available on how CRP or other inflammatory biomarkers can change in severe cases [ 6 ].…”