AsianScientist (Oct. 12, 2018) – In a study published in Scientific Reports, scientists in Japan have developed a method to observe the formation of atherosclerotic plaques in living mice.
Atherosclerosis, involving the buildup of plaque in the arteries and an associated reduction in the flow of blood, is a major feature of cardiovascular diseases. While researchers have obtained a better understanding of how these plaques build up in the body, being able to track the actual accumulation of plaques has remained a challenge.
In the present study, researchers at the University of Tsukuba, Japan, have developed a tool that can image the development of atherosclerotic plaque in the body and follow its progression over time. This could enable accurate evaluation of drugs to treat atherosclerosis.
The team first induced atherosclerosis in mice by inactivating a fat and cholesterol-related receptor and feeding them on a high-cholesterol diet. They also exposed these mice to X-rays to wipe out the native cells of their immune system, then transplanted fluorescent immune cells into the mice.
“The main advantage of our approach is that the introduced immune cells, the macrophages, congregate in atherosclerotic plaques, so the level of fluorescence emitted by them strongly correlates with the amount of plaque that has formed,” said study leader Assistant Professor Yoshihiro Miwa of the University of Tsubaka.
“Because the expressed fluorescent proteins emit light in the near-infrared part of the spectrum, they can be detected at deeper locations within the body, such as the thoracic aorta.”
The researchers also sought to confirm that their method can be used to identify the amount of atherosclerotic plaque within the mice, rather than just detect the presence or absence of plaque. To do so, they established three different experimental groups of mice with differing feeding patterns. Mice were fed a high-cholesterol diet every day, or a high-cholesterol diet and a normal diet on alternate weeks, or just a normal diet.
The team reported that the intensity of the fluorescent signal increased with the duration and frequency of high-cholesterol diet consumption, which in turn reflects the accumulation of plaques over time.
“Because we can now clearly analyze the amount of plaque present and how it changes over time, our work should lead to more effective monitoring of how well anti-atherosclerotic drugs work,” said study corresponding author Dr. Michito Hamada of the University of Tsubaka.
“This method can also reduce the number of experimental animals used because there’s no need to sacrifice them and remove tissues for analysis at each time point within an experiment.”
The team hopes to further increase the sophistication of this tool, which could potentially lead to accurate analysis of the risk associated with the buildup of plaque in human patients, as well as facilitate the development of novel therapeutics for the condition.
The article can be found at: Kulathunga et al. (2018) A Novel iRFP-Incorporated in vivo Murine Atherosclerosis Imaging System.
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Source: University of Tsukuba; Photo: Pixabay.
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