Severe acute pancreatitis is associated with upregulation of the ACE2-angiotensin-(1-7)-Mas axis and promotes increased circulating angiotensin-(1-7)

Pancreatology. 2012 Sep-Oct;12(5):451-7. doi: 10.1016/j.pan.2012.07.017. Epub 2012 Aug 9.

Abstract

Background/objectives: Angiotensin-converting enzyme 2 (ACE2), its product angiotensin-(1-7) and its receptor Mas may counteract the adverse effects of the ACE-angiotensin receptor II-AT(1) axis in many diseases. We examined the expression of these novel components of the rennin-angiotensin system in an experimental mouse model of severe acute pancreatitis (SAP).

Methods: SAP was induced by six intraperitoneal injections of caerulein, and mice were sacrificed at 2, 12, 24, 48 and 72 h post disease-induction (normal control group mice were sacrificed at 2 h post disease-induction). Tissue and blood were collected for biochemical detection, gene and protein expression by qRT-PCR and western blot analysis, enzyme-linked immunosorbent assay and immunohistology detection.

Results: Pancreatic ACE2 gene and protein expression, plasma and pancreatic angiotensin-(1-7) levels and Mas receptor gene and protein expression were significantly increased (p < 0.05) following SAP induction compared with the normal control group.

Conclusions: Severe acute pancreatitis is associated with upregulation of the ACE2-angiotensin-(1-7)-Mas axis and promotes increased circulating angiotensin-(1-7). These results support the presence of an ACE2-angiotensin-(1-7)-Mas axis in pancreatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Angiotensin I / blood*
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Ceruletide
  • Disease Models, Animal
  • Male
  • Mice
  • Pancreas / metabolism
  • Pancreatitis / chemically induced
  • Pancreatitis / physiopathology*
  • Peptide Fragments / blood*
  • Peptidyl-Dipeptidase A / physiology*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / physiology*
  • Receptors, G-Protein-Coupled / physiology*
  • Renin-Angiotensin System / physiology*
  • Up-Regulation

Substances

  • Peptide Fragments
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Receptors, G-Protein-Coupled
  • Ceruletide
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2
  • angiotensin I (1-7)