Related Experiment Video

Updated: Jun 6, 2026

Quantification of Atherosclerosis in Mice
06:59

Quantification of Atherosclerosis in Mice

Published on: June 12, 2019

11β-hydroxysteroid dehydrogenase type 2 deficiency accelerates atherogenesis and causes proinflammatory changes in

Graeme A Deuchar1, Danielle McLean1, Patrick W F Hadoke1

  • 1Centre for Cardiovascular Science, The Queen's Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.

Endocrinology
|November 26, 2010
PubMed

Insights

Loss of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) causes mineralocorticoid receptor (MR) activation, leading to accelerated atherosclerosis. MR antagonism protects against plaque development and inflammation in mice.

Area of Science:

  • Cardiovascular Biology
  • Endocrinology
  • Molecular Medicine

Background:

  • Mineralocorticoid receptor (MR) activation promotes inflammation and atherosclerosis.
  • 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) normally inactivates glucocorticoids, preventing inappropriate MR activation.
  • Understanding the role of MR and 11β-HSD2 in atherogenesis is crucial for cardiovascular disease treatment.

Purpose of the Study:

  • To investigate whether glucocorticoid-mediated MR activation contributes to atheromatous plaque formation.
  • To determine the specific mechanisms by which 11β-HSD2 deficiency impacts atherosclerosis.
  • To evaluate the therapeutic potential of MR antagonism in preventing atherosclerosis.

Main Methods:

  • Generation of Apoe(-/-)/11β-HSD2(-/-) double-knockout (E/b2) mice to model loss of 11β-HSD2 function.
  • Analysis of atherosclerotic lesion development, plaque composition (macrophages, lipids, collagen), and endothelial activation markers.
  • Pharmacological intervention with an MR antagonist (eplerenone) and an epithelial sodium channel blocker (amiloride).

Main Results:

  • E/b2 mice developed significant atherosclerotic lesions by 3 months, unlike control Apoe(-/-) mice.
  • E/b2 mouse plaques exhibited increased macrophages and lipids, with reduced collagen.
  • Eplerenone treatment reduced plaque burden and inflammation, increasing collagen and smooth muscle cells.
  • Amiloride showed a less pronounced atheroprotective effect compared to eplerenone.
  • Vascular cell adhesion molecule 1 expression was elevated in E/b2 mice endothelium.

Conclusions:

  • Loss of 11β-HSD2 leads to MR activation and promotes significant atherogenesis.
  • MR activation stimulates proinflammatory processes in the endothelium, contributing to plaque development.
  • MR antagonism represents a promising therapeutic strategy for atherosclerosis, independent of blood pressure reduction.

More Related Videos

Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice07:36

Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice

Published on: September 26, 2018

Related Concept Videos

Atherosclerosis I: Introduction01:30

Atherosclerosis I: Introduction

Atherosclerosis is a progressive disorder characterized by the buildup of plaques on the arterial inner wall, causing them to narrow and harden over time. These plaques comprise lipids, calcium, blood components, carbohydrates, and fibrous tissue. The process primarily affects the intima of large and medium-sized arteries, reducing blood flow in any artery.Etiology and risk factorsThe cause of atherosclerosis is multifactorial, involving a complex interplay among endothelial injury, lipid...
Coronary Artery Disease II: Pathophysiology01:26

Coronary Artery Disease II: Pathophysiology

Coronary Artery Disease (CAD) originates from a series of events that impair the function of coronary arteries, the blood vessels responsible for delivering oxygen-rich blood to the heart muscle. The pathophysiology of CAD is closely linked to atherosclerosis, a chronic inflammatory and lipid-driven condition affecting the vascular endothelium.1. Endothelial DamageThe process begins with damage to the vascular endothelium, which serves as a protective barrier between the blood and the vessel...
Inflammation01:38

Inflammation

Overview
Coronary Artery Disease I: Introduction01:30

Coronary Artery Disease I: Introduction

Coronary Artery Disease (CAD): An Overview with Scientific InsightsCoronary Artery Disease (CAD), often referred to as C-A-D, is a prevalent blood vessel disorder classified under the broader category of atherosclerosis. Atherosclerosis is a pathological process characterized by the hardening and narrowing of arteries due to the accumulation of atherosclerotic plaques. These plaques are composed of cholesterol, fatty substances, inflammatory cells, calcium, and fibrin, reducing blood flow to...
Type II Diabetes II: Pathophysiology01:24

Type II Diabetes II: Pathophysiology

PathophysiologyType 2 diabetes mellitus (T2DM ) is a chronic metabolic disorder characterized by insulin resistance and progressive pancreatic β-cell dysfunction, leading to impaired glucose homeostasis. It results from interactions among genetic predisposition, environmental factors, and metabolic stressors, such as overnutrition and a sedentary lifestyle.Insulin Resistance and Glucose DysregulationEarly T2DM involves insulin resistance in skeletal muscle, adipose tissue, and the liver.
Peripheral Artery Disease I: Introduction01:30

Peripheral Artery Disease I: Introduction

Peripheral artery disease (PAD) predominantly results from atherosclerosis, which involves the accumulation of fatty deposits, or plaques, within the walls of arteries. This causes them to narrow and harden, significantly reducing blood flow. PAD predominantly affects the legs, particularly the arteries supplying the thighs and calves. In rare cases, it may involve other arteries, including those in the arms.Etiology of PAD:The principal cause of PAD is atherosclerosis, which results from fatty...