Progression of atherosclerosis is marked by growing plaques of dead cells, oxidized LDL cholesterol, and two types of immune cells: T lymphocytes and dendritic cells, which are responsible in part for chronic inflammation in addition to their normal immune functions. To study in further detail how statins interact with the immune system, Karolinska Institutet scientists set out to determine the interaction between T lymphocytes and dendritic cells.
They did so by looking directly at atherosclerotic plaques obtain from human patients undergoing surgery. They found that oxidized LDL cholesterol activated inflammatory T lymphocytes from the plaque through the dendritic cells, but in the presence of statins, the process was interrupted. Statins blocked the inflammatory T lymphocytes, instead stimulating the production of regulatory T lymphocytes, which mediate the inflammatory response. Additionally, statins recharged the dendritic cells so they were anti-inflammatory.
"For the first time, we're able to show that an immunological treatment for atherosclerosis can actually work,” said professor Johan Frostegard of the study’s significance.
However, Frostegard is no stranger to the potential negative side effects of statins. Past studies have shown that these drugs have carcinogenic properties in certain circumstances due to their repression of gene activators, called microRNAs. Specifically, statins repress let7c, which normally inhibits tumor growth. In the current study, researchers found let7c to be associated with oxidized LDL-induced T lymphocyte activation. Nevertheless, Frostegard believes statin drugs to be safe in most situations.
"If a patient has a tumor in which let7c plays an important part, the statin effect could be adverse,” Frostegard explained. “At the same time, statins reduce inflammation and that can lower the risk of cancer, and large metastudies show no general increase in cancer risk."
Frostegard’s study was recently published in The Journal of the American Heart Association.
Sources: Karolinska Institutet, Food and Drug Administration, University of Maryland Medical Center