University of Kentucky researchers have discovered a possible added benefit of a novel new drug that lowers blood pressure.
Dr. Lisa Cassis and Dr. Alan Daugherty found in animal studies* that aliskiren not only lowered blood pressure but also significantly reduced artery-clogging lesions that are the leading cause of heart attack and stroke, the top cause of death worldwide.
"In my many years of atherosclerosis research, this is one of the most striking effects I have seen on preventing the disease under experimental conditions," Daugherty said. "This contributes to our knowledge of the underlying disease that causes heart attack and stroke."
Aliskiren, marketed under the brand name Tekturna by pharmaceutical manufacturer Novartis, is the first new class of blood pressure medication approved by the FDA in more than a decade. Approved a year ago, it acts differently than any other medication currently on the market by inhibiting renin, an enzyme that is primarily produced in the kidneys. Renin is the first step in the synthesis of one of the most important molecules in blood pressure regulation.
Renin inhibition in mice with profound hypercholesterolemia was found to reduce the size of the artery hardening atherosclerotic plaques. Macrophages are cells that play a critical role in the development of atherosclerotic plaques and they were shown to produce proteins of the RAS system.
Further analysis indicated that when the bone marrow of mice with hypercholesterolemia was replaced with that of renin-deficient mice, a procedure that favors the production of renin-deficient macrophages, atherosclerotic plaque sizes were reduced.
The authors therefore concluded that macrophage-derived renin plays an important role in the development of atherosclerotic plaques.
"Our data shows that renin inhibition is an effective approach to both lowering blood pressure and directly inhibiting atherosclerosis. It will be interesting to determine whether this approach is more effective than the two other commonly used classes of drugs in the angiotensin system; ACE inhibitors and ARBs," Daugherty said.
*Cassis is director of the UK Graduate Center for Nutritional Sciences and Daugherty is director of the UK Cardiovascular Research Center.
Journal reference: Renin inhibition reduces hypercholesterolemia-induced atherosclerosis in mice. Journal of Clinical Investigation. February 14, 2008.
This research was funded in part by Novartis Institutes for Biomedical Research.
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