In a new Yale-led study, investigators have revealed previously unknown factors that contribute to the hardening of arteries and plaque growth, which cause heart disease. Their insight is the basis for a promising therapeutic approach to halt and potentially reverse plaque buildup and the progression of disease, the researchers said.
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. To understand the factors contributing to this inflammation, the research 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 cultured human cells, the researchers discovered that TGF? 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 TGF? induced inflammation in these cells in mouse models. This finding was notable, said the researchers, because TGF? proteins are known to decrease inflammation in other cells in the body.
The researchers also showed that when the TGF? receptor gene is deleted in endothelial cells, both the inflammation and plaque in blood vessels are significantly reduced.
To test this approach as a potential therapy, the team, led by professor of medicine Michael Simons, M.D., used an “interfering” RNA, or RNAi, drug developed at Yale, to disrupt TGFß receptors. Interfering RNA use a gene’s own DNA sequence to turn off or silence the gene. To deliver the drug only to endothelial cells in the blood vessel walls of mice, they employed microscopic particles, or nanoparticles, created by their co-authors at MIT. This strategy reduced inflammation and plaque as effectively as the genetic technique.
The findings identify TGFß signaling as a major cause of chronic vessel wall inflammation, and demonstrate that disruption of this pathway leads to cessation of inflammation and substantial regression of existing plaque, said the scientists.
Based on this discovery, investigators 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 Latest on: Atherosclerosis
via Google News
The Latest on: Atherosclerosis
- Examining a Possible Link Between Atherosclerosis and Inflammationon November 19, 2020 at 2:36 pm
Unfortunately, this inflammation can damage the site even further, which occurs quite often in cardiovascular disease. Atherosclerosis is a cardiovascular disease that occurs when fats build up and ...
- Jose Ordovás, PhD, on Body Size and Its Effect on Subclinical Atherosclerosis Prevalenceon November 19, 2020 at 7:59 am
Body size affects the prevalence of subclinical atherosclerosis (SA), suggesting medication and other lifestyle changes could improve cardiac risk in those who fall into a riskier body-size category, ...
- Association between periodontal disease and atherosclerosis in patients with rheumatoid arthritison November 18, 2020 at 6:23 pm
Among 197 patients with rheumatoid arthritis, those with antibody responses to common periodontal pathogens were more likely to also show signs of atherosclerosis. Evidence of exposure to a particular ...
- Evinacumab in Patients with Refractory Hypercholesterolemiaon November 18, 2020 at 2:58 am
have an increased risk of atherosclerosis. In such patients, the efficacy and safety of subcutaneous and intravenous evinacumab, a fully human monoclonal antibody against angiopoietin-like 3 ...
- Atherosclerosis: Symptoms, Causes, Treatment And Tips To Prevent by Dr Viveka Kumaron November 17, 2020 at 6:09 am
Atherosclerosis is a health problem that bothers many people. Know the causes, symptoms, treatment and tips to prevent from a cardiologist. Atherosclerosis is a very broad term which means that ...
- Brilinta reduced the composite of stroke and death…on November 17, 2020 at 2:40 am
we are pleased to see that aspirin plus ticagrelor has the potential to be an effective preventive treatment for subsequent stroke in patients with cervicocranial atherosclerosis.” ...
- Analysis of genes and underlying mechanisms involved in foam cells formation and atherosclerosis developmenton November 16, 2020 at 3:59 pm
(D) Venn diagram showing the overlap of DEGs in the ox-LDL-treated SMCs (with downregulated and upregulated trends overtime obtained by STEM analysis) and atherosclerosis-related genes, which were ...
- Tomocube’s HT-2 microscope quantifies therapeutic effects of targeted nanodrugs against atherosclerosison November 16, 2020 at 10:59 am
Treatment of Atherosclerosis, the disease responsible for approximately half of all deaths in westernized societies, is a step closer following correlative studies using Tomocube’s HT-2 microscope.
- 15 Foods That May Help Prevent Clogged Arterieson November 15, 2020 at 4:00 pm
Atherosclerosis occurs when fatty deposits accumulate along artery walls. You may have heard the condition referred to as clogged arteries or a hardening of the arteries. This causes the arteries ...
- New screening questionnaire can identify people at high risk of developing heart diseaseon November 14, 2020 at 8:57 am
A new study in a Swedish population of middle-aged adults found that four out of 10 people have atherosclerosis, a buildup of fatty deposits that reduce blood flow to the heart. Early detection of ...
via Bing News