Inflammation in response to bad cholesterol LDL → accelerates the progression of arteriosclerosis
A group of ‘regulatory T cells’-like T cells develops a tendency to attack specific lipoproteins
La Jolla Institute of Immunology, USA, thesis in ‘Nature Cardiovascular Research’
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Atherosclerosis is a vascular disease in which atherosclerotic plaques accumulate on the endothelium of arteries and the blood vessels narrow and lose elasticity.
That is why atherosclerosis is sometimes called atherosclerosis (粥狀硬化症).
Atherosclerotic plaque (粥狀硬化斑) is a mixture of fat, cholesterol, calcium, etc.
When these plaques accumulate in the arterial endothelium, oxygen-carrying blood cannot be properly delivered to organs or tissues, leading to coronary artery disease, stroke, myocardial infarction, and peripheral arterial disease.
When endothelial cells proliferate while plaque is deposited, a hard membrane surrounds the atheroma. A blood clot is formed when this membrane ruptures.
T cells are also deeply involved in atherosclerosis. Inflammation of T cells is known to exacerbate this type of arteriosclerosis.
However, scientists at the La Jolla Institute of Immunology (LJI) in the United States have found out which types of T cells actually cause arterial inflammation and through which mechanisms.
It was found that a specific group of T cells, which are apparently similar to ‘regulatory T cells’ (Tergs), attack ‘apolipoprotein B’ (abbreviated ‘apo B’) and cause inflammation.
Apo B is a key component of ‘LDL’ (low-density lipoprotein), which is harmful to the body.
This finding is expected to be of great help in the treatment and early diagnosis of arteriosclerosis, which is the number one cause of death from disease in developed countries.
The results of this study conducted by Professor Klaus Lee’s team at LJI’s Autoimmune Inflammation Center were recently published in the journal Nature Cardiovascular Research.
Inflammation caused by T cells affects the deposition of atherosclerotic plaques in the cardiovascular system.
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According to the outline of papers posted on the American Association for the Advancement of Science (AAAS) site (www.eurekalert.org) on the 24th, it is as difficult as ‘finding a needle in a haystack’ to find T cells involved in atherosclerosis in the blood.
This is because T cells that do this are extremely rare.
However, it was already known that high levels of LDL in the blood can cause harmful plaque to build up in the arterial endothelium.
The build-up of these plaques can cause inflammation, block blood flow, and cause a stroke or myocardial infarction (heart attack).
This time, Professor Lee’s team confirmed for the first time that T cells directly attack ‘Apo B’ of LDL.
This can cause inflammation and worsen atherosclerosis.
In the mouse experiment, the phenomenon of ‘T cell expansion’ appeared first.
Then, as ‘apo B’ reactive T cells in the blood increased, arteriosclerosis became more severe.
Once atherosclerosis started, ‘apo-B’ reactive T cells showed a tendency to become more and more aggressive.
Professor Lee’s team analyzed 12,000 T cells using single-cell RNA sequencing (sequencing analysis) and T-cell receptor sequencing technology in cooperation with researchers from Albert Einstein Medical University.
Blood samples were donated from eight female patients in their 50s and 60s.
The scientists screened 110 T cells that identified ‘Apo B’ as targets.
These T cells looked like ‘regulatory T cells’ that regulate inflammation, but did not behave like regulatory T cells.
Instead, as heart disease progressed, these T cells formed a new identity.
This means that it has the characteristic of causing inflammation by attacking the apolipoprotein of LDL.
Inflammatory immune cells (green) from obese mice surround adipocytes (red).
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This study is the first to elucidate the pro-inflammatory behavior of T cells involved in atherosclerosis in detail.
It goes without saying that this finding will help treat cardiovascular diseases such as arteriosclerosis in the future.
Prospects are also raised that it will revolutionize the early diagnosis and severity of heart disease.
Of course, a test method that precisely selects this type of T cell by analyzing a blood sample must first be developed.
The research team is also interested in developing a vaccine to prevent atherosclerosis by inhibiting the activation of dangerous T cells.
In particular, Professor Li hopes to analyze more blood samples from cardiovascular patients for follow-up studies.
This is because it was quite difficult to obtain appropriate patient blood samples while conducting this study.
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