Potential Role of ADAMTS13 in the Progression of Alcoholic Hepatitis
| Autor: | Tomomi Matsuyama, Tatsuhiro Tsujimoto, Masahito Uemura, Hitoshi Yoshiji, Yoshihiro Fujimura, Hiroshi Fukui, Hiromichi Ishizashi, Chie Morioka, Masao Fujimoto, Seiji Kato, Masatoshi Ishikawa, Masanori Matsumoto |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Platelet Aggregation
Multiple Organ Failure Thrombotic thrombocytopenic purpura ADAMTS13 Protein Alcoholic hepatitis Pathogenesis hemic and lymphatic diseases von Willebrand Factor medicine Humans Platelet Liver injury Hepatitis Alcoholic business.industry Microcirculation Thrombosis medicine.disease ADAMTS13 Pathophysiology ADAM Proteins Psychiatry and Mental health Liver Immunology Disease Progression Hepatic stellate cell Cytokines Protein Multimerization business Liver Failure |
| Zdroj: | Current Drug Abuse Reviewse. 1:188-196 |
| ISSN: | 1874-4737 |
| DOI: | 10.2174/1874473710801020188 |
| Popis: | Alcoholic hepatitis (AH) is a potentially life-threatening complication of alcohol abuse. The severe form of AH, severe alcoholic hepatitis (SAH), is characterized by multiorgan failure (MOF) with manifestations of acute hepatic failure and is associated with high morbidity and mortality. However, the pathogenesis of SAH in addition to AH remains to be elucidated. Recent advances showed that ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13) is closely related to thrombotic thrombocytopenic purpura, a multiorgan disorder. Decreased activity of plasma ADAMTS13 (ADAMTS13:AC) leads to the accumulation of unusually large von Willebrand factor multimers (UL-VWFM) and subsequent platelet clumping and/or thrombi under high shear stress, resulting in microcirculatory disturbances. Immunological studies and in situ hybridization have indicated that ADAMTS13 is produced exclusively in hepatic stellate cells (HSCs). Plasma ADAMTS13:AC was extremely low in fatal SAH cases, and enhanced UL-VWFM production with deficient ADAMTS13:AC may contribute to the progression of MOF through microcirculatory disturbances in SAH and AH. Considering that ADAMTS13 is synthesized in HSCs and its substrate, UL-VWFM, is produced in transformed vascular endothelial cells, the imbalance between ADAMTS13:AC and VWF:Ag in AH patients might also involve sinusoidal microcirculatory disturbances and subsequent liver injury. It will be necessary to clarify the mechanism of the decrease in plasma ADAMTS13:AC in association with pro-inflammatory cytokinemia, an ADAMTS13 inhibitor and the production of ADAMTS13 in HSCs. The determination of ADAMTS13:AC and its substrate will give us new insights into the pathophysiology of acute alcoholic liver injury and help to elucidate additional therapeutic strategies for this disease. |
| Databáze: | OpenAIRE |
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