Inducing Myointimal Hyperplasia Versus Atherosclerosis in Mice: An Introduction of Two Valid Models

Summary

This video shows two models of intimal plaque development in murine arteries and emphasizes the differences in myointimal hyperplasia and atherosclerosis.

Abstract

Various in vivo laboratory rodent models for the induction of artery stenosis have been established to mimic diseases that include arterial plaque formation and stenosis, as observed for example in ischemic heart disease. Two highly reproducible mouse models – both resulting in artery stenosis but each underlying a different pathway of development – are introduced here. The models represent the two most common causes of artery stenosis; namely one mouse model for each myointimal hyperplasia, and atherosclerosis are shown. To induce myointimal hyperplasia, a balloon catheter injury of the abdominal aorta is performed. For the development of atherosclerotic plaque, the ApoE -/- mouse model in combination with western fatty diet is used. Different model-adapted options for the measurement and evaluation of the results are named and described in this manuscript. The introduction and comparison of these two models provides information for scientists to choose the appropriate artery stenosis model in accordance to the scientific question asked.

Introduction

In industrialized nations ischemic heart disease remains a leading cause of mortality¹. The causes for coronary artery stenosis are manifold and include myointimal hyperplasia as well as atherosclerosis, with revascularization remaining the most common treatment strategy². Research models that clearly distinguish between the mechanistic pathways of intimal hyperplasia and atherosclerosis are essential to investigate the pathobiological and pathophysiological processes in arterial plaque development. In this video two different mouse models used to study either the development of myointimal hyperplasia or atherosclerosis are introduced.

Protocol

All animal work should be carried out according to relevant animal care guidelines. Obtain institutional approval for animal work prior to beginning protocol.

1. Myointimal Hyperplasia Model (A)

For the intimal hyperplasia model, purchase C57BL/6J (Stock number 000664, C57BL/6J) mice at the age of 8 weeks weighing approximately 25 g. House mice for these experiments under conventional conditions; feed mice standard mouse chow and provide water ad libitum.

1. Mouse preparation: Introduce the mouse to an anesthetic state with isoflurane (2%) utilizing an induction chamber. ....

Results

Figure 1 shows different analysis options and the induced disease state for both models. For the intimal hyperplasia model, the analysis of representative cross sections in trichrome staining is shown. From these cross sections, results like I/M ratios, maximum plaque thickness, maximum intimal thickness in the lumen, luminal obliteration in percent, as well as plaque area can be measured and calculated.

To evaluate the outcome of the atherosclerosis model, all methods named a.......

Discussion

Although both diseases result in similar symptoms in the patient, the underlying mechanisms of plaque development and therefore the treatment approaches are very different². In different forms of arterial stenosis the clinical findings in the patients as well as the timeframe of plaque development depend on the underlying mechanism.

Depending on the clinical findings in the patient, different methods of sample analysis must be performed^5,15. It is necessary to adapt the a.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Thyoglycollate Broth 3%	Fluka	70157	powder
PFA 4%	Electron Microscopy Sciences	#157135S	20%
Sudan III staining solution	Sigma Aldrich	S4131	powder
mouse C57BL/6J	Jackson Laboratories	Stock # 0006664
mouse ApoE -/-	Jackson Laboratories	Stock #002052
Western Diet	Harlan Laboratories	TD.88137
hair clipper	WAHL	8786-451A ARCO SE
Forene	Abbott		Isoflurane
microsurgical clamp	Fine Science Tools	18055-04	Micro-Serrefine - 4 mm
clamp applicator	Fine Science Tools	18056-14
catheter
10-0 prolene suture	Ethicon	788G
6-0 prolene suture	Ethicon	8709H
5-0 prolene suture	Ethicon	EH7229H
Rimadyl	Pfizer		Carprofen
Metacam 1.5 mg/ml	Boehringer Ingelheim		Metamizol