MADRID, Feb. 21 (EUROPE PRESS) –
Researchers at Brigham and Women’s Hospital, Harvard Medical School, have discovered, using a preclinical model of atherosclerosis, a long and non-coding RNA (ARNIC) that can point the way to new therapies for atherosclerosis and shed light on by what the probability of the disease increases with age, as published in the journal ‘Science Translational Medicine’.
Once discarded as ‘junk DNA’, approximately 75 percent of the human genome does not encode proteins. But these dark regions of the genome are far from being garbage, but they can have tempting clues about disease states.
A team of Brigham researchers led by Mark Feinberg, of the Division of Cardiovascular Medicine and associate professor of Medicine at Harvard Medical School, recently submerged in these regions in search of clues about atherosclerosis, a disease in which arteries become increasingly hardened and narrow, obstructing blood flow and causing heart disease.
“We have identified a new actor to control aging in the vessel wall and, surprisingly, it is not a traditional gene or protein. It is part of the non-coding genome. That was unexpected,” says Feinberg. “We know a lot about the importance of cholesterol and inflammation in heart disease, but this is a new and additional route. We need to think carefully about how it could affect the development of therapies for cardiovascular disease. “
Feinberg and his colleagues used a mouse model of atherosclerosis in which mice begin to develop atherosclerotic lesions at 12 weeks.
The researchers isolated RNA from the innermost lining of the blood vessel wall and analyzed the entire genome in all RNAs, looking for which had changes in activity during disease progression or regression. One of the most dynamic was SNHG12, a long stretch of RNA that does not encode a protein but is found in multiple species, including humans, pigs and mice.
To better understand the role of SNHG12, the researchers conducted experiments in which they reduced their activity or intensified it. They found that less SNHG12 led to a profound increase in atherosclerosis, but more SNHG12 dramatically reduced disease progression.
To understand what SNHG12 was doing, the team looked for who their partners were. One of them turned out to be a molecule involved in the repair of DNA damage and aging. Without these partners working together, the vessel walls became permeable and permeable to bad cholesterol. The team could reverse this phenomenon by adding a small molecule that promotes DNA damage repair, suggesting a possible therapeutic route to follow.
“What is really exciting is that RNA therapy, in which we deliver RNA molecules or small molecules that can help regulate RNA, is a growing area,” Feinberg points out. “Our work helps lay the groundwork. to carry out this type of therapy for atherosclerosis. “
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