Researchers have for the first time demonstrated how the main protein of low-density lipoprotein (LDL), commonly referred to as 'bad cholesterol', binds to its receptor. The findings were published in the esteemed journal Nature.
This discovery sheds light on the mechanism by which cholesterol contributes to the development of heart disease, currently the leading cause of death worldwide. It also offers new alternatives in the search for effective treatments and paves the way for personalized therapies.
In the bloodstream, LDL attaches to a receptor protein known as LDLR, initiating the process of cholesterol clearance. However, genetic mutations can hinder this function, leading to cholesterol accumulation in the arteries and resulting in vessel blockage.
The study's authors utilized cryo-electron microscopy, an advanced imaging technology, to observe this process. For the first time, they were able to visualize the entire structural protein of LDL as it binds to LDLR.
Subsequently, using artificial intelligence software developed by the 2024 Nobel Prize winners in Chemistry, they identified the genetic mutations responsible for the dysregulation of cholesterol clearance.
This molecular-level observation of the binding process opens new avenues for developing effective treatments for high cholesterol. By understanding precisely how this connection occurs, researchers can create new drugs that target these specific points to enhance LDL clearance from the bloodstream.
Additionally, experts discovered that many of the mutations involved in the LDL-LDLR binding were associated with familial hypercholesterolemia, a hereditary condition characterized by defects in the absorption of low-density cholesterol by cells. Individuals with this condition often exhibit high levels of this substance in their blood and face an increased risk of heart attacks at a young age.
Cardiologist Pâmela Assunção from Ebserh (Brazilian Hospital Services Company) emphasizes the importance of being aware of family history, particularly regarding early heart disease in first-degree relatives. She states, 'Familial hypercholesterolemia affects patients very early on. The sooner and longer treatment is initiated, the easier it is to reduce risk levels.'
High cholesterol levels contribute to cardiovascular disease, increasing the likelihood of plaque formation and acute conditions such as heart attacks and strokes, as well as chronic issues like angina and intermittent claudication. Moreover, it raises mortality risk and decreases life expectancy.
A study conducted last year revealed that heart attacks could reduce remaining life expectancy by up to 11 years, especially in patients under 50 and women. This research followed over 330,000 individuals from 1991 to 2022.
Assunção notes a concerning rise in heart attack cases due to atherosclerosis among adults and young people in Brazil. She advocates for preventive measures, emphasizing the importance of a healthy diet and regular physical activity.
Last year, U.S. researchers monitored the dietary habits of 459 adults aged 22 to 75 over eight weeks, dividing them into three groups: one followed a control diet, another consumed a diet rich in fruits and vegetables, and the third adhered to the DASH diet, known for its emphasis on whole foods, low-fat dairy, and reduced sodium intake.
Both the DASH diet and the fruit-and-vegetable-rich diet reduced the risk of atherosclerotic cardiovascular disease by about 10%, primarily due to lower blood pressure. These results highlight the effectiveness of simple lifestyle changes, which can yield substantial benefits in just eight weeks.
To prevent atherosclerosis, Paula Schmidt, a professor and researcher at Unesp (São Paulo State University), recommends maintaining a balanced diet that includes fruits, vegetables, lean meats like fish and chicken, and whole grains rich in fiber. Trans fats should be avoided entirely, and saturated fats should be limited to less than 10% of daily calories.