Cholesterol ‘crystals’ studied for role in heart attack, stroke
Thanks to the work of George S. Abela, MD, MSc, MBA, professor at Michigan State University, and his colleagues, there are new advances in the war against heart attacks and strokes to celebrate during National Heart Month in February.
In recent studies, he demonstrated that early in the disease commonly known as “hardening of the arteries,” or atherosclerosis, dangerous cholesterol crystals are formed. He found that several factors can cause crystallization, including a high cholesterol saturation, a drop in ambient temperature (even by a few degrees centigrade), a shift in the pH favoring alkaline levels, and the hydration of the cholesterol molecule to the monohydrate form.
“Furthermore,” explains Abela, “a combination of these seems to exceed the individual effect, so that a drop in temperature in a saturated solution will greatly enhance crystallization.” The end result is that the cholesterol expands in volume when crystallizing to form sharp tipped crystals that can cut through the arterial wall and plaque to cause a heart attack. “The formation of crystals also is an alert to the immune system to activate damaging inflammation of the arteries,” says Abela.
Given this new perspective on the role of cholesterol crystals in atherosclerosis, Abela and his colleagues have explored whether certain medications known to protect from heart attacks and strokes have an effect on cholesterol crystals. “Because statins – a class of drugs that inhibits certain enzymes – are the most widely used agent to lower serum levels of cholesterol, we proceeded to test the effect of statins on cholesterol crystallization,” says Abela.
“Initially, we evaluated the effect of statins on cholesterol crystallization in a test tube and demonstrated that these drugs did indeed reduce both the volume and the crystallization of cholesterol. This is a direct effect of statins (atorvastatin; simvastatin; pravastatin) on cholesterol crystals and it was dose-related,” he says. “Also, it is known from clinical studies that statins given during a heart attack or angioplasty reduces the risk of further tissue injury.”
Currently, a clinical trial (CANTOS: Canakinumab Anti-inflammatory Thrombosis Outcomes Study) by Novartis Pharmaceutical is being performed, based on Abela and his team’s work on cholesterol crystals. This study is evaluating the effect of an anti-inflammatory agent (Canakinumab, a monoclonal antibody that inhibits IL-1β) in blocking the molecular signals initiated by cholesterol crystals. While the clinical data are not yet available, their hypothesis is that blocking the inflammatory response will eventually reduce inflammation in the arterial plaque – and reduce the risk for heart attacks and stroke.
Similarly, alcohol dissolves cholesterol crystals and, according to Abela, clinical data demonstrates cardio protection by alcohol when it is used in moderation. “We are studying these effects to better understand how this process works,” he says. For Abela and his colleagues, every month is dedicated to a future with healthier hearts.
Dr. Abela is laboratory director, and professor and chief of the Division of Cardiology, for the College of Human Medicine at Michigan State University, as well as program director for the Cardiovascular Fellowship Training Program. He is a fellow of the American College of Cardiology, National Lipid Association, and American Heart Association.