Clinical Characteristics, Serum Biochemical Changes, and Expression Profile of Serum Cfa-miRNAs in Dogs Confirmed to Have Congenital Portosystemic Shunts Accompanied by Liver Pathologies

Ahmed M El-Sebaey,Pavel N Abramov,Fatma M Abdelhamid

doi:10.3390/vetsci7020035

Abstract

Computed tomography angiography (CTA) and biochemical parameters cannot specify liver pathologies in dogs with congenital portosystemic shunts (CPSS) that are easily determined by invasive histopathology. This study aims to assess the possibility of using circulating serum canine familiaris (cfa) microRNAs (miRNAs) as novel non-invasive serum-based fingerprints for liver injuries associated with various morphologies of extrahepatic and intrahepatic portosystemic shunts (EHPSS and IHPSS). Data were obtained from 12 healthy dogs and 84 dogs confirmed to have EHPSS (splenocaval, splenophrenic, splenoazygos, right gastrocaval (RGC), right gastrocaval with caudal loop (RGC–CL)) and IHPSS (right divisional and left divisional) using CTA. Hepatic pathologies were determined by histopathology. Serum expression of miRNAs was assessed by real-time polymerase chain reaction. Based on the nature of liver injuries in each shunt type, cfa-miR-122 was significantly upregulated in all CPSS groups. Meanwhile, serums cfa-miR-34a and 21 were not significantly expressed in splenophrenic or splenoazygos groups, but they were extensively upregulated in splenocaval, RGC, RGC–CL groups and less frequently in right or left divisional groups. Also, serum cfa-miR126 was significantly upregulated in both IHPSS groups but less significantly expressed in RGC, RGC–CL, and splenocaval groups. Overall, estimated cfa-miRNAs could serve as novel biomarkers to mirror the histopathological and molecular events within the liver in each shunt type.

Highlights

Congenital portosystemic shunts (CPSS) are considering the most frequent vascular abnormality of the hepatobiliary system in dogs (Canis lupus familiaris)
Most of the dogs affected either with EHPSS or IHPSS were presented with signs of intermittent vomition, whereas, neurological signs after feeding as well as the sign of stranguria and hematuria were most commonly reported in dogs with splenocaval, RGC and RGC-CL shunts as well as the two morphologies of IHPSS
Dogs affected either with splenophrenic and splenoazygos shunts surprisingly diagnosed at a mean age significantly higher than all examined groups, while dogs affected with the two morphologies of IHPSS diagnosed at an age significantly lower than all investigated groups

Summary

Introduction

Congenital portosystemic shunts (CPSS) are considering the most frequent vascular abnormality of the hepatobiliary system in dogs (Canis lupus familiaris). CPSS conjoins the portal vein with the caudal vena cava (CVC) or azygos vein, allowing blood from the portal circulation (incorporated with toxins, hepatotrophic substances, and nutrients) to bypass the hepatic parenchyma and flow directly into the circulation system [1]. Inducing hepatic dysfunction [2], as well as circulatory persistence of neurotoxic substances typically metabolized by the liver, such as ammonia, give rise to a wide variety of clinical signs and serum biochemical and histological abnormalities [3,4]. Thereupon, the surgical attenuation of the shunting vessel is the gold standard to redirect portal blood into hepatic tissue to promote normalization of hepatic structure and function [5].

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