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Updated: May 15, 2026

Quantification of Atherosclerosis in Mice
06:59

Quantification of Atherosclerosis in Mice

Published on: June 12, 2019

Reciprocal regulation of cholesterol excretion in apolipoprotein E-null mice by angiotensin II type 1 and type 2

Masaru Iwai1, Hisako Sone, Harumi Kanno

  • 1Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime, Japan.

Life Sciences
|January 22, 2013
PubMed
Abstract

Insights

Angiotensin (AT) receptor deficiency impacts cholesterol excretion. AT(1) receptor deficiency increases fecal cholesterol, while AT(2) receptor deficiency decreases it, suggesting reciprocal regulation in high-cholesterol conditions.

Area of Science:

  • Cardiovascular Research
  • Metabolic Regulation
  • Pharmacology

Background:

  • Atherosclerosis is a complex disease involving lipid metabolism.
  • The renin-angiotensin system, including AT(1) and AT(2) receptors, plays a role in cardiovascular function.
  • Understanding the role of these receptors in cholesterol homeostasis is crucial for managing atherosclerosis.

Purpose of the Study:

  • To investigate the effects of AT(1) and AT(2) receptor deficiency on cholesterol intake and excretion.
  • To elucidate the reciprocal roles of AT(1) and AT(2) receptors in cholesterol metabolism during high-cholesterol diet conditions.

Main Methods:

  • Utilized apolipoprotein E-null (ApoEKO) mice, a model for atherosclerosis.
  • Generated AT(1)a/ApoEKO and AT(2)/ApoEKO mice to study receptor deficiency.
  • Administered a high-cholesterol diet (HCD) and analyzed plasma, fecal, and bile cholesterol levels.
  • Examined liver cholesterol content and gene expression of HMG-CoA reductase and LDL receptor.
  • Investigated the effect of an AT(1) receptor blocker (irbesartan) on cholesterol excretion in ApoEKO mice.

Main Results:

  • AT(1)a/ApoEKO mice showed lower plasma cholesterol and higher fecal/bile cholesterol compared to ApoEKO mice.
  • AT(2)/ApoEKO mice exhibited higher plasma cholesterol and lower fecal/bile cholesterol.
  • Liver cholesterol content and key enzyme expression remained unchanged among groups.
  • Irbesartan treatment increased bile cholesterol and tended to increase fecal cholesterol excretion in ApoEKO mice on HCD.

Conclusions:

  • AT(1) and AT(2) receptor stimulation reciprocally regulate cholesterol excretion into bile and feces.
  • These receptors play a significant role in cholesterol homeostasis, particularly under conditions of cholesterol overload.
  • Targeting AT(1) receptors may offer a therapeutic strategy for enhancing cholesterol excretion in atherosclerosis.

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