By Drs. David Niesel and Norbert Herzog
Atherosclerosis, sometimes called hardening of the arteries, affects about 5 million people in the US. This disease results from the accumulation of plaque inside arteries. The development of plaque is linked to elevated levels of cholesterol in the blood. The buildup of plaque leads to different diseases including coronary heart disease, carotid artery disease and peripheral artery disease. Most interventions to prevent these diseases rely on reducing the amount of cholesterol in the blood. Now come some tantalizing results that an FDA-approved substance that is used to improve the delivery of other drugs can actually solubilize cholesterol and dissolve the plaques.
The majority of the cholesterol in the blood is contained in low-density lipoprotein, or LDL, which serves to transport it from the liver to other tissues and cells. LDL-cholesterol is also known as the "bad" cholesterol for its role in atherosclerosis. The second type is high-density lipoprotein, or HDL, cholesterol is known as the "good" cholesterol since it seems to guard against heart problems by recycling cholesterol back to the liver for excretion.
Monocytes are a type of white blood cell that serve as wandering scavengers to ingest foreign substances as part of our immune system. These monocytes also participate in atherosclerosis by taking up residence in arterial walls where they consume lipids or fats. The progression of atherosclerosis depends of the concentration of LDL-cholesterol in the blood. The LDL-cholesterol undergoes a process called oxidation and becomes toxic which initiates inflammation. Continued plaque growth results from accumulation of more LDL-cholesterol, causing the enlargement of the external elastic membrane in the artery. As the LDL-cholesterol accumulation continues, the plaque causes the narrowing of the artery diameter. Various forces can cause plaques to rupture, which initiates the formation of a thrombus or clot. This clot may block the artery causing an abrupt loss of blood flow. In the heart, partial blockage leads to angina, or chest pain, while complete blockage can cause a myocardial infraction or heart attack. Currently, drugs only can lower blood cholesterol levels but none reduce the plaques once they have formed.
Scientists had evidence that a simple sugar molecules called 2-hydroxypropyl-β-cyclodextrin could increase the solubility of cholesterol and promote its removal. Cyclodextrin is safe and is added to a large number of commercial foods and is also is used to solubilize other drugs for delivery to the body. Scientists fed groups of mice a high cholesterol diet for eight weeks with one group receiving injections of cyclodextrin while a control group did not. Amazingly, cyclodextrin-treated mice were far less affected by plaques than control mice. Cyclodextrin-treated mice eliminated excess cholesterol and also had reduced levels of the inflammation that leads to atherosclerosis. Plaques that had been surgically removed from human atherosclerotic arteries were placed in petri dishes containing nutrient growth medium. When cyclodextrin was added to the petri dish, the cholesterol in the plaques became soluble and disappeared into the medium. Inflammation was also reduced and together this suggests cyclodextrin might also be effective in humans. This tantalizing data must be confirmed and followed up with clinical studies to evaluate whether cyclodextrin can be used to reverse the atherosclerotic process and improve human health.
Could it really be that simple? We certainly hope so.
Medical Discovery News is hosted by professors Norbert Herzog at Quinnipiac University, and David Niesel of the University of Texas Medical Branch. Learn more at www.medicaldiscoverynews.com.