Name: inducing myointimal hyperplasia versus atherosclerosis in mice: an introduction of two valid models
Uploaded: 2014-05-14T13:00:00
Description: Watch this Scientific Journal Video about Inducing Myointimal Hyperplasia Versus Atherosclerosis in Mice: An Introduction of Two Valid Models at JoVE.com

The authors thank Christiane Pahrmann for technical assistance. S.S. received funding from the Deutsche Forschungsgemeinschaft (DFG) (SCHR992/3-2 and SCHR992/4-2).

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 ...

<ol>
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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 performed5,15. It is necessary to adapt the a...

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.
Myointimal hyperplasia is postulated to form via the &#8220;response-to-injury&#8221; paradigm originally described for atherosclerosis3. The mechanical disruption of the endothelial layer leads to an intense remodeling enhanced by paracrine effects. There are several different animal models commonly used to study myointimal hyperplasia. Some groups use metal devices in the ascending aorta of rats4. The aortic denudation model performed with a balloon catheter is also commonly used in laboratory rats5,6. The intimal hyperplasia model performed in laboratory mice7 implements ligation of the carotid artery and induces myointimal lesions8. In our lab, the abdominal aortic denudation model &#8211; to study the development of myointimal hyperplasia &#8211; as well as a humanized stent restenosis model9 are commonly used. This video emphasizes that choosing the proper experimental animal model is crucial for mechanistic or pathophysiologic studies of arterial stenosis.
Myointimal hyperplasia models must be distinguished from atherosclerosis models. For the latter, apolipoprotein E-deficient (ApoE -/-) mice in combination with western diet are commonly used to induce atherosclerotic lesions10,11,12,13. Examples for the induction of both of these types of myointimal disease in mice are shown here, along with different model-adapted options to analyze vessel stenosis14.

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			<td style="width:140px;">Comments</td>
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			<td height="17" style="height:17px;">Thyoglycollate Broth 3%</td>
			<td>Fluka</td>
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			<td>powder</td>
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			<td height="17" style="height:17px;">PFA 4%</td>
			<td>Electron Microscopy Sciences</td>
			<td>#157135S</td>
			<td align="right">20%</td>
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			<td height="17" style="height:17px;">Sudan III staining solution</td>
			<td>Sigma Aldrich</td>
			<td>S4131</td>
			<td>powder</td>
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			<td height="17" style="height:17px;">mouse C57BL/6J</td>
			<td>Jackson Laboratories</td>
			<td>&#160;Stock # 0006664</td>
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			<td>Abbott</td>
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			<td>Isoflurane</td>
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			<td height="17" style="height:17px;">microsurgical clamp</td>
			<td>Fine Science Tools</td>
			<td>18055-04</td>
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			<td height="17" style="height:17px;">6-0 prolene suture</td>
			<td>Ethicon</td>
			<td>8709H</td>
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			<td height="17" style="height:17px;">5-0 prolene suture</td>
			<td>Ethicon</td>
			<td>EH7229H</td>
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			<td height="17" style="height:17px;">Rimadyl</td>
			<td>Pfizer&#160;</td>
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			<td>Carprofen</td>
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			<td height="17" style="height:17px;">Metacam 1.5mg/ml</td>
			<td>Boehringer Ingelheim</td>
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			<td>Metamizol</td>
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inducing myointimal hyperplasia versus atherosclerosis in mice: an introduction of two valid models

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&#160;&#8211;&#160;both resulting in artery stenosis but each underlying a different pathway of development&#160;&#8211; 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.

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...

Watch this Scientific Journal Video about Inducing Myointimal Hyperplasia Versus Atherosclerosis in Mice: An Introduction of Two Valid Models at JoVE.com

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

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

Various in vivo laboratory rodent models for the induction of artery stenosis have been established to mimic diseases that include arterial plaque ...

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