Understanding cholesterol and heart disease is now more complex
Results of a new study show that an entire network of events can occur that leads to heart disease and heart attack, making understanding cholesterol more complex. High cholesterol levels was once believed to be the sole culprit for blocked arteries, but now researchers, using sophisticated equipment, find that much goes on inside the artery walls at a cellular level that can inflame and produce plaque and heart blockages. Understanding the role of cholesterol in heart disease is now more complicated than previously known, though inflammation is widely implicated for causing heart attack.
New studies show a clearer picture of how one class of immune cells goes awry in response to cholesterol, setting off a chain of events that cannot be attributed to just high levels of LDL (bad) cholesterol. According to research author Jay W. Heinecke, of University of Washington, the findings are remarkable. "Despite 30 years of study, we still don't know how cholesterol causes heart disease." Understanding heart disease is difficult, but now researchers are a bit closer to finding out how atherosclerosis that leads to heart attack develops.
According to the study, macrophages are already known to play a role in the development of heart disease. They are cells that destroy bacteria and remove debris and play a role in immune function. In the past, scientists believed cholesterol moving in and out of macrophages caused overload. Plaque in the arteries was believed to occur when there was too much buildup in the arteries for macrophages to remove.
New research shows an entire network of macrophage activity becomes disrupted and leads to heart disease. "It's definitely a different way to think about what is going on," Heinecke says. Proteins that work together and are already known, called a macrophage sterol-responsive network (MSRN) are found in microvesicles outside the macrophage cells. Macrophages turn into foam cells that look exactly like they sound. The scientists now see that anything that disrupts the way the macrophage network works can lead to heart disease.
In studies, the researchers found that even mice lacking LDL receptors, cholesterol lowering drugs known as statins restored the macrophage network to almost normal. Mice without single proteins in the network, including APOE and so-called complement proteins of the immune system were also found to have foam cells associated with plaque buildup and heart disease that were not loaded with cholesterol.
The study authors concluded, "We propose that the atherogenic actions of cholesterol-loaded macrophages are an emergent property that results when the normal balance of MSRN proteins in microvesicles is perturbed. We further suggest that certain dietary factors or genetic variations can disturb this network, thereby promoting vascular disease. By integrating mouse and human data, we hope to better understand the MSRN's role in foam cell formation, with the long-term goal of identifying therapeutic interventions for targeting networks rather than individual proteins."
Heinecke says anything that disrupts the macrophage or MSRN network, can promote heart disease and heart attack. A better means of preventing heart disease might lie in targeting the entire network of proteins by restoring proper function rather than simply trying to lower cholesterol. Understanding the role of cholesterol and heart disease has become more complicated, but somewhat clearer from the study.