Why Don't Rodents Develop Atherosclerosis?

Atherosclerosis is a condition in which plaque builds up in the walls of the arteries. This plaque is made up of cholesterol, fatty materials, fibers, calcium, and other substances found in the blood. While humans commonly experience the effects of atherosclerosis, rodents, including mice, do not appear to develop this condition naturally. In this article, we will explore the reasons behind this phenomenon, focusing on the differences in cholesterol metabolism between humans and rodents, as well as the utility of mouse models in the study of experimental atherosclerosis.

The Role of Cholesterol in Atherosclerosis

Cholesterol is a waxy, fat-like substance found in the bloodstream and cells of the body. Although both humans and rodents have cholesterol, it is the way in which this cholesterol is processed and carried by the body that distinguishes the pathology of atherosclerosis.

Cholesterol and Lipoproteins in Humans

Humans carry about 75% of their plasma cholesterol as low-density lipoprotein (LDL). LDL is often referred to as "bad" cholesterol because an excess of LDL can lead to the accumulation of plaque in the arteries, a hallmark of atherosclerosis. The remaining 25% of human plasma cholesterol is carried by high-density lipoprotein (HDL), often referred to as "good" cholesterol, which helps to remove excess cholesterol from the bloodstream and reduce the risk of atherosclerosis.

Cholesterol and Lipoproteins in Mice

Mice, on the other hand, carry most of their cholesterol on HDL. Unlike humans, mice primarily utilize HDL for cholesterol transport, which is actually protective against the development of atherosclerosis. This difference in lipoprotein composition between humans and mice is a key factor in explaining why rodents do not naturally develop atherosclerosis.

Mouse Models of Experimental Atherosclerosis

Despite their natural resistance to atherosclerosis, mice have become valuable subjects in the study of this condition. Scientists use genetically modified mice and other experimental models to simulate the development of atherosclerosis. Here are some of the most widely used mouse models:

Transgenic Mice

Transgenic mice are genetically engineered to have specific changes in their genes that lead to an increased risk of developing atherosclerosis. These mice are used to study the molecular mechanisms involved in the disease and to test potential treatments. Examples of such models include the apoE knockout mouse, which lacks the gene for apolipoprotein E, a protein involved in cholesterol transport.

Diets and Induced Atherosclerosis

Another approach to study atherosclerosis in mice is to induce the condition through diet. Feeding mice a high-fat diet can lead to the development of atherosclerotic plaques in the arteries, mimicking the natural progression of the disease in humans. This model allows researchers to study the effects of dietary factors on atherosclerosis and to test the efficacy of potential therapeutic interventions.

Conclusion

The absence of atherosclerosis in rodents, particularly in mice, can be attributed to their unique cholesterol metabolism and the protective role of HDL in their bodies. However, the mouse models used in scientific research have significantly contributed to our understanding of atherosclerosis and the development of potential treatments. These models are crucial for identifying and testing new therapeutic strategies to combat this disease, which remains a major health concern for humans.

Keywords

rodents, atherosclerosis, cholesterol, LDL, HDL