Characterization of a murine model of endothelial dysfunction induced by chronic intraperitoneal administration of angiotensin II

Sci Rep. 2021 Oct 27;11(1):21193. doi: 10.1038/s41598-021-00676-x.

Abstract

Endothelial dysfunction (ED) is a key factor for the development of cardiovascular diseases. Due to its chronic, life-threatening nature, ED only can be studied experimentally in animal models. Therefore, this work was aimed to characterize a murine model of ED induced by a daily intraperitoneal administration of angiotensin II (AGII) for 10 weeks. Oxidative stress, inflammation, vascular remodeling, hypertension, and damage to various target organs were evaluated in treated animals. The results indicated that a chronic intraperitoneal administration of AGII increases the production of systemic soluble VCAM, ROS and ICAM-1 expression, and the production of TNFα, IL1β, IL17A, IL4, TGFβ, and IL10 in the kidney, as well as blood pressure levels; it also promotes vascular remodeling and induces non-alcoholic fatty liver disease, glomerulosclerosis, and proliferative retinopathy. Therefore, the model herein proposed can be a representative model for ED; additionally, it is easy to implement, safe, rapid, and inexpensive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / administration & dosage*
  • Angiotensin II / toxicity
  • Animals
  • Disease Models, Animal*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology
  • Infusions, Parenteral
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukins / metabolism
  • Kidney / metabolism
  • Kidney / pathology
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress
  • Transforming Growth Factor beta / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Cell Adhesion Molecule-1 / metabolism
  • Vascular Diseases / etiology
  • Vascular Diseases / metabolism*
  • Vascular Diseases / pathology
  • Vascular Remodeling

Substances

  • Interleukins
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Angiotensin II
  • Intercellular Adhesion Molecule-1