The effects of hepatic steatosis on thromboxane A2 induced portal hypertension

Gastroenterol Hepatol. 2019 Nov;42(9):534-541. doi: 10.1016/j.gastrohep.2019.03.015. Epub 2019 Jul 17.
[Article in English, Spanish]

Abstract

Introduction and aim: Thromboxane (TX) A2 was identified as an important vasoconstrictor during Zymosan induced portal perfusion pressure (PP) increase. We aimed at investigating whether hepatic steatosis influences the extent of TXA2-induced portal hypertension.

Materials and methods: Sprague-Dawley rats were randomly divided into control and steatosis (induced by the special diet) groups. PP and TXB2 (stable degradation product of TXA2) in the perfusate were measured after in situ liver perfusion with Zymosan (150μg/ml, 40-46min) or U46619 (TXA2 analog, 0.1μM/ml, 40-46min). The number of Kupffer cell (KC) was measured by immunohistochemistry with CD163.

Results: Zymosan induced more TXB2 production and a higher PP increase in control group than in steatosis group despite more CD163 positive KCs in fatty livers. PP and TXB2 efflux revealed a strong correlation in control group and a moderate correlation in steatosis group. Contrary to the effect of Zymosan, U46619 induced a much higher PP increase in steatosis group than in control group.

Conclusion: Severe steatosis increased number of KCs, however, PP increase and TXB2 efflux caused by Zymosan infusion in fatty livers were lower than those in healthy livers. In contrast, TXA2 analog caused higher PP increase in fatty livers. Targeting the more sensitive response to TXA2 in fatty livers might be a potential therapy of severe steatosis.

Keywords: Células de Kupffer; Esteatohepatitis no alcohólica; Kupffer cells; Nonalcoholic steatohepatitis; Rat; Rata; Zymosan.

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
  • Animals
  • Antigens, CD / analysis
  • Antigens, Differentiation, Myelomonocytic / analysis
  • Cell Count
  • Diet, High-Fat
  • Fatty Liver / complications*
  • Fatty Liver / pathology
  • Fatty Liver / physiopathology
  • Hypertension, Portal / chemically induced*
  • Kupffer Cells / chemistry
  • Kupffer Cells / cytology
  • Perfusion / methods
  • Portal Pressure / drug effects*
  • Portal Pressure / physiology
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface / analysis
  • Thromboxane A2 / analogs & derivatives
  • Thromboxane B2 / analysis
  • Thromboxane B2 / biosynthesis*
  • Vasoconstrictor Agents
  • Zymosan / pharmacology*

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • Receptors, Cell Surface
  • Vasoconstrictor Agents
  • Thromboxane B2
  • Thromboxane A2
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Zymosan