In a new study, NYU Langone Medical Center researchers have discovered how cholesterol-lowering drugs called statins promote the breakdown of plaque in the arteries. The study was published online by the journal PLoS One on December 6, 2011.
The findings support a large clinical study that recently showed patients taking high-doses of the cholesterol-lowering medications not only reduced their cholesterol levels but also reduced the amount of plaque in their arteries. However, until now researchers did not fully understand how statins could reduce atherosclerosis, the accumulation of fat and cholesterol that hardens into plaque in arteries, a major cause of mortality in Western countries. High blood cholesterol is a major culprit in atherosclerosis. As a result of narrowing arteries, blood clots can form or plaque can break off causing blockages in vessels. This can lead to a potentially fatal heart attack or stroke.
"Our new research shows statins actually promote the regression of atherosclerosis by altering the expression of a specific cell surface receptor within plaque cells," said co-author of the study, Edward Fisher, MD, PhD, Leon H. Charney Professor of Cardiovascular Medicine and director of the Marc and Ruti Bell Vascular Biology Program at NYU Langone Medical Center. "This molecular phenomenon helps dissolve plaque by expelling coronary artery disease-causing cells from the plaque lining the arteries."
The NYU Langone study reveals how statins promote the transformation of arterial plaques by activating a protein that sits on the surface of macrophages, immune cells that are prevalent in plaque. The immune system sends macrophages to clean up cholesterol deposits in arteries, but once they fill up with the bad form of cholesterol they get stuck in the arteries, triggering the body's inflammatory response. The bloated macrophages then become major components of plaque lining artery walls.
In the study, researchers show in mouse models that statins activate the cell surface protein receptor C-C chemokine receptor type 7 (CCR7), which in turn activates a cell-signaling pathway forcing macrophages out of plaque. In addition, the researchers show that macrophages only leave plaque when CCR7 is expressed. Therefore, regression of plaque is dependent on CCR7, the researchers concluded. The statins appeared to directly regulate and enhance CCR7 gene expression and induce macrophage cells to leave the plaque. CCR7 is a widely studied protein associated with the migration of immune cells and its expression is a marker of the presence of macrophages.
Statins are potent inhibitors of HMG-CoA reductase, the enzyme that plays a central role in the production of cholesterol. Statins have been shown to reduce the risk of cardiovascular disease and cardiac events like heart attack. Cholesterol is needed for all proper cellular function. High-density lipoprotein cholesterol (HDL-C), good cholesterol, helps reduce the risk of atherosclerosis by taking cholesterol away from cells. Low density lipoprotein (LDL-C), bad cholesterol, carries cholesterol to cells. However, an LDL overload in the body increases a person's risk of cardiovascular disease including atherosclerosis.
"Our experimental findings indicate that statins, in addition to lowering LDL cholesterol, have clinical benefits of accelerating plaque regression by a newly discovered mechanism," said co-author Michael Garabedian, PhD, Professor, Department of Microbiology and Urology at NYU Langone Medical Center. "It's possible that these drugs could possibly be more beneficial to a wider population of patients potentially reducing the overall lifetime burden of plaque and the prevention of atherosclerosis."
The study was a collaboration by NYU Langone Medical Center's Department of Medicine, Division of Cardiology, the Department of Microbiology, Schneider Children's Medical Center of Israel and the Centre for Clinical Pharmacology, Division of Medicine at the University College of London in the United Kingdom. This research study was supported by funding from the National Institutes of Health, Astra Zeneca and Pfizer.
About NYU Langone Medical Center
NYU Langone Medical Center, a world-class, patient-centered, integrated, academic medical center, is one on the nation's premier centers for excellence in clinical care, biomedical research and medical education. Located in the heart of Manhattan, NYU Langone is composed of three hospitals – Tisch Hospital, its flagship acute care facility; the Rusk Institute of Rehabilitation Medicine, the world's first university-affiliated facility devoted entirely to rehabilitation medicine; and the Hospital for Joint Diseases, one of only five hospitals in the nation dedicated to orthopaedics and rheumatology – plus the NYU School of Medicine, which since 1841 has trained thousands of physicians and scientists who have helped to shape the course of medical history. The medical center's tri-fold mission to serve, teach and discover is achieved 365 days a year through the seamless integration of a culture devoted to excellence in patient care, education and research. For more information, go to www.NYULMC.org.
Lauren Woods | EurekAlert!
Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences