Imaging Fibrogenesis in a Diet-Induced Model of Nonalcoholic Steatohepatitis (NASH)
| Autor: | Edward G. Robins, R. Boominathan, Siddesh V. Hartimath, Fui Fong Yong, X. Deng, Peng Wen Tan, Peter Cheng, W. Han, Vanessa Soh, Yong Chun Chong, Julian L. Goggi |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Liver Cirrhosis
Male Pathology medicine.medical_specialty Fluorine Radioisotopes lcsh:Medical technology Article Subject Diet High-Fat Severity of Illness Index 030218 nuclear medicine & medical imaging Extracellular matrix 03 medical and health sciences Liver disease Mice 0302 clinical medicine Fibrosis Non-alcoholic Fatty Liver Disease Hepatic Stellate Cells Medicine Animals Radiology Nuclear Medicine and imaging RNA Messenger Triglycerides Clinical pathology business.industry Histology Organ Size medicine.disease Integrin alphaVbeta3 Imaging agent Actins Choline Deficiency Mice Inbred C57BL Hydroxyproline Early Diagnosis lcsh:R855-855.5 Gene Expression Regulation Liver 030220 oncology & carcinogenesis Positron-Emission Tomography Hepatic stellate cell Disease Progression Collagen Steatosis Radiopharmaceuticals business Research Article |
| Zdroj: | Contrast Media & Molecular Imaging Contrast Media & Molecular Imaging, Vol 2019 (2019) |
| ISSN: | 1555-4309 |
| DOI: | 10.1155/2019/6298128 |
| Popis: | Purpose. Liver fibrosis is the hallmark of chronic nonalcoholic steatohepatitis (NASH) and is characterised by the excessive deposition of extracellular matrix proteins. Early detection and accurate staging of liver fibrosis is critically important for patient management. One of the earliest pathological markers in NASH is the activation of hepatic stellate cells (HSCs) which may be exploited as a marker of fibrogenesis. Activated HSCs secreting factors such as integrin αvβ3 propagate fibrosis. The purpose of the current study was to assess the utility of the integrin αvβ3 imaging agent [18F]FtRGD for the early detection of fibrosis in a diet-induced model of NASH longitudinally using PET imaging. Procedures. Mice were fed with either standard chow diet (SD), high-fat diet (HFD), or a choline-deficient, L-amino acid-defined high-fat fibrogenic diet (CDAHFD) to mimic the clinical pathology of liver disease and followed longitudinally for 10 weeks to assess the development of liver fibrosis using [18F]FtRGD positron emission tomography (PET) imaging. Standard blood biochemistry, histological measures, and qPCR were used to quantify integrin αvβ3, smooth muscle actin, and collagen types 1 and 6 to assess the extent of NASH pathology and accurately stage liver fibrosis. Results. The CDAHFD fibrogenic diet predictably developed hepatic inflammation and steatosis over the 10 weeks studied with little NASH pathology detected in high fat diet-treated animals. Stage 1 fibrosis was detected early by histology at day 21 and progressed to stage 2 by day 35 and stage 3 by day 56 in mice fed with CDAHFD diet only. Noninvasive imaging with [18F]FtRGD correlated well with integrin αvβ3 and was able to distinguish early mild stage 2 fibrosis in CDAHFD animals compared with standard chow diet-fed animals at day 35. When compared with high fat diet-fed animals, [18F]FtRGD was only able to distinguish later moderate stage 2 fibrosis in CDAHFD animals at day 49. Conclusions. The diet-induced progression of liver fibrosis was confirmed using histology and correlated well with the mRNA of integrin αvβ3 and extracellular matrix protein expression. [18F]FtRGD showed very good correlation between liver uptake and integrin αvβ3 expression and similar detection sensitivity to the current clinical gold standard modalities for staging of liver fibrosis. |
| Databáze: | OpenAIRE |
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