In a new study, researchers have revealed previously unknown factors that contribute to the hardening of arteries and plaque growth, which cause heart disease.
The new finding is the basis for a promising therapy to halt and potentially reverse plaque buildup and the progression of the disease.
The research was led by Yale University.
Current treatments for plaque and hardened arteries, a condition known as atherosclerosis, can slow but not improve the disease.
Experts believe that may be due to ongoing inflammation in blood vessels.
In the study, the team focused on a group of proteins, called transforming growth factor beta (TGFß), that regulates a wide range of cells and tissues throughout the body.
Using human cells, the researchers discovered that TGFβ proteins trigger inflammation in endothelial cells—the cells that form the inner lining of artery walls—but not in other cell types.
With a technique called single-cell RNA-seq analysis, which measures the expression of every gene in single cells, they then showed that TGFβ induced inflammation in these cells in mouse models.
This finding was important because TGFβ proteins are known to decrease inflammation in other cells in the body.
The researchers also showed that when the TGFβ receptor gene is deleted in endothelial cells, both the inflammation and plaque in blood vessels are reduced.
To test this approach as a potential therapy, the team used an “interfering” RNA, or RNAi, a drug developed at Yale, to disrupt TGFß receptors.
Interfering RNA uses a gene’s own DNA sequence to turn off or silence the gene.
They found this strategy reduced inflammation and plaque as effectively as the genetic technique.
The team says TGFß signaling as a major cause of chronic vessel wall inflammation.
The disruption of this pathway leads to the cessation of inflammation and substantial regression of existing plaque.
The researchers at Yale and MIT have launched a biotech company, VasoRX, Inc., to develop this targeted approach, using the RNAi drug delivered by nanoparticles as a potential therapy for atherosclerosis in people.
The lead author of the study is a professor of medicine Michael Simons, M.D.
The study is published in Nature Metabolism.
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