Heart disease is the leading cause of death for men and women in the United States, which highlights the urgent need for new strategies to prevent the condition. Researchers may be one step closer to meeting this need, after locating a gene that assists in the clearance of excess cholesterol from blood vessels.
The gene — known as MeXis — was previously believed to sit under the umbrella of “selfish” genes, or those thought to be functionless because they fail to produce proteins.
But the new study shows that MeXis does not need to produce proteins to be useful. Instead, it makes molecules known as long-coding RNAs (IncRNAs).
These IncRNAs regulate the expression of a protein that removes cholesterol from the arteries.
High cholesterol is a major risk factor for heart disease.
Lead study author Dr. Tamer Sallam, the co-director of the Center for Cholesterol Management at the University of California, Los Angeles (UCLA), and his colleagues recently reported their new findings in the journal Nature Medicine.
According to the Centers for Disease Control and Prevention (CDC), around 610,000 people in the United States die from heart disease every year.
Coronary artery disease (CAD), which is also called coronary heart disease, is the most common form of heart disease, accounting for around 370,000 deaths annually. CAD is caused by the accumulation of plaque in the arteries.
Over time, plaque buildup can block the arteries and reduce the flow of blood to the heart, which is a process known as atherosclerosis. This can lead to chest pain, or angina, irregular heartbeat, heart attack, and heart failure.
High cholesterol — more specifically, high low-density lipoprotein (LDL) cholesterol — is a major risk factor for heart disease. When we consume too much cholesterol from our diet, it can accumulate in the arteries.
In the new study, Dr. Sallam and colleagues discovered how the MeXis gene helps to remove excess cholesterol from the arteries, potentially opening the door to a new strategy for heart disease prevention.
With their new study — which was conducted using mice — the researchers sought to learn more about the molecular events that play a role in atherosclerosis.
They identified MeXis as a key player; plaque accumulation in the blood vessels of rodents without the gene was almost double that of mice with normal levels of MeXis.
Upon further investigation, the team found that MeXis activates the expression of a protein called Abca1 through the production of IncRNAs. The role of Abca1 is to remove excess cholesterol from the blood vessels.
It was found that increasing MeXis levels in the rodents led to an increase in the removal of cholesterol from blood vessels, which makes MeXis a potential candidate for heart disease prevention and treatment.
What is more, the findings may open the door to other genes that play a role in heart health.
“What this study tells us is that lncRNAs are important for the inner workings of cells involved in the development of heart disease,” says senior study author Dr. Peter Tontonoz, of the David Geffen School of Medicine at UCLA.
“Considering many genes like MeXis have completely unknown functions,” he explains, “our study suggests that further exploring how other long non-coding RNAs act will lead to exciting insights into both normal physiology and disease.”
In future research, the team plans to find out more about the mechanisms of MeXis, how its activity can be modified, and whether it could hold up as a target for heart disease prevention.
“The idea that lncRNAs are directly involved in very common ailments such as plaque buildup within arteries offers new ways of thinking about how to treat and diagnose heart disease.”
Dr. Tamer Sallam
“There is likely a good reason why genes that make RNAs rather than proteins exist,” Dr. Sallam continues. “A key question for us moving forward is how they may be involved in health and disease.”