Newly discovered connection leads to atherosclerosis and heart disease – healing practice

Significant advances in understanding of atherosclerosis

Now, for the first time, a connection has been identified between mitochondria, inflammation and a pair of genes that are considered a risk factor for the development of atherosclerosis applies, which in turn can lead to life-threatening heart attacks and strokes.

In a study involving experts from University of California – San Diego became the connection between two genes (DNMT3A and TET2), mitochondrial function, inflammation and atherosclerotic plaque formation. The results are published in the journal “Immunity“ published.

What happens when DNMT3A and TET2 are mutated?

DNMT3A and TET2 designate a pair of genes that regulate the growth of blood cells. But there is one Mutation before, the gene pair is associated with an increased risk of developing atherosclerosis connected, report the experts.

We found that the genes DNMT3A and TET2, in addition to their normal role (…), directly activate the expression of a gene involved in mitochondrial inflammatory pathways, suggesting a new molecular target for atherosclerosis therapies‘ explains the author of the study Dr. Gerald Shadel in a press release.

How do DNMT3A and TET2 mutations lead to atherosclerosis?

When the researchers investigated the role played by DNMT3A and TET2 mutations in what is known as clonal hematopoiesis, they found that abnormal inflammatory signals associated with DNMT3A and TET2 deficiency in blood cells inflammatory response play, which promotes the development of atherosclerosis.

However, the question arose as to how exactly the DNMT3A and TET2 genes are involved in inflammation and atherosclerosis. “The problem was that we couldn’t figure out how DNMT3A and TET2 are involved because the proteins they encode seem to do opposite things in terms of DNA regulation“, says study author Professor Dr. Christopher Glass.

This antagonistic activity of the genes led the researchers to suspect that other mechanisms could play a role. This prompted the team to take a new approach.

Years ago, another research group led by Dr. Shadel references the inflammatory pathway now observed when examining reactions mitochondrialen DNA-Stress uncovered. A unique subset of cell DNA resides in the mitochondria.

The team around Dr. Shadel studied the effects of mitochondrial DNA stress by removing a gene (TFAM) that contributes to the mitochondrial DNA properly packaged becomes. The researchers found that by reducing the TFAM level mitochondrial DNA expelled from the mitochondria into the interior of the cell.

This triggers the same molecular alarm signals The researchers explain which cells warn of a bacterial or viral invader and trigger a molecular defense pathway that triggers an inflammatory response.

Why do mutations cause inflammatory reactions?

In cooperation, the research groups around Professor Dr. Glass and Dr. Shadel now have a better understanding of why DNMT3A and TET2 mutations occur inflammatory reactions lead that are similar to those at mitochondrialem DNA-Stress to be watched.

The teams looked at cells from people with normal cells, from people with loss-of-function mutations in DNMT3A or TET2 expression, and additionally from people with atherosclerosis.

What triggers an increased inflammatory response?

It turned out that experimentally reducing the expression of DNMT3A or TET2 in normal blood cells produced similar results as in blood cells with loss-of-function mutations and in blood cells from people with atherosclerosis. In all three cases there was one increased inflammatory response.

How exactly was the inflammation triggered?

In addition, the experts observed that low levels of DNMT3A and TET2 expression in blood cells lead to a decreased TFAM expression led. As a result, a abnormal mitochondrial DNA packaging formed, which triggered inflammation due to the released mitochondrial DNA.

Which increases plaque formation in atherosclerosis

We discovered that DNMT3A and TET2 mutations prevent their ability to bind and activate the TFAM gene. The absence or reduction of this binding activity leads to the release of mitochondrial DNA and an overactive mitochondrial inflammatory response‘ explains the author of the study Dr. Isidoro Cobo.

According to the research team, this process can exacerbate plaque formation in atherosclerosis. (as)

Author and source information

This text corresponds to the specifications of medical specialist literature, medical guidelines and current studies and has been checked by medical professionals.

Sources:

  • Isidoro Cobo, Tiffany N. Tanaka, Kailash Chandra, Mangalhara Addison, Lana Calvin Yeang, et al.: DNA methyltransferase 3 alpha and TET methylcytosine dioxygenase 2 restrain mitochondrial DNA-mediated interferon signaling in macrophages; in: Immunity (veröffentlicht 04.08.2022), Immunity
  • University of California – San Diego: Mitochondrial DNA Mutations Linked to Heart Disease Risk (veröffentlicht 04.08.2022), University of California – San Diego

Important NOTE:
This article contains general advice only and should not be used for self-diagnosis or treatment. He can not substitute a visit at the doctor.

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