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Mineola, NY - January 13, 2009 - Researchers at Winthrop-University Hospital have discovered why arthritis patients treated with a drug known as Methotrexate (MTX) appear to be protected against cardiovascular disease. In addition, they have identified the specific mechanism by which MTX helps the body to clear cholesterol from patients' arteries, and may therefore shed important new light on potential new treatments for heart disease, as well as a way to ameliorate the increased cardiac risk induced by certain other powerful anti-inflammatory medications.
Allison Reiss, M.D., Head of the Inflammation Section of the Division of Rheumatology, Allergy and Immunology at Winthrop-University Hospital, colleague Steven E. Carsons, M.D., Chief of the hospital's Division of Rheumatology, Allergy and Immunology, and their collaborators recently published an important new paper in Arthritis & Rheumatism, an official monthly journal of the prestigious American College of Rheumatology. The title of the article, which appears in the December 2008 edition, is "Atheroprotective Effects of Methotrexate on Reverse Cholesterol Transport of Proteins and Foam Cell Transformation in Human THP-1 Monocyte/ Macrophages."
This study was aimed at finding ways to overcome the atherogenic effect and resulting cardiovascular risks associated with once-popular COX-2 inhibitor drugs such as Vioxx and Bextra, both of which were withdrawn from the market in 2004. The Winthrop researchers' goal is to discover ways to reduce or eliminate the increase in cardiac events associated with these drugs while retaining their valuable pain-relieving and anti-inflammatory benefits.
Drs. Reiss and Carsons' work on methotrexate, one of the most effective and commonly used medicines to treat rheumatoid arthritis and other rheumatic conditions, has been recognized as a major advance in autoimmune research.
It was known that MTX decreases the pain and swelling of arthritis and can reduce damage to joints and the risks of long-term disability. However, what Dr. Reiss and Dr. Carsons discovered was that MTX promotes elimination of cholesterol from the arteries and could therefore limit potential, life-threatening build up of atherosclerotic plaque. "This discovery is the first evidence that any readily available medication can increase expression of anti-atherogenic proteins to counteract the negative effects of COX-2 inhibitors, while maintaining their very beneficial effects," said the authors of the research paper.
"Many older patients who are in need of pain relief are also vulnerable to heart disease," said Dr. Reiss. "We are working to develop new treatment options for pain that do not elevate heart attack risk. While focusing on patients with autoimmune disorders, the insights we gain can be applied to improve cardiovascular outcomes in general."
The MTX research project was supported by a grant from the National Institutes of Health (NIH)/National Heart, Lung and Blood Institute and by an Innovative Research Grant from the Arthritis Foundation (see below).
Major New Research Grant
Principal investigator Allison Reiss, M.D., was recently awarded a two-year $190,000 "Innovative Research Grant" from the national Arthritis Foundation, the only national non-profit that supports arthritis research. Dr. Reiss' research grant proposal, titled "Atherosclerosis in Rheumatoid Arthritis and Lupus: Restoring Cholesterol Balance," was ranked in the top five proposals nationwide.
In order to earn substantial research grants such as the NIH grant that funded the MTX research project or the two-year $190,000 "Innovative Research Grant" recently awarded to Dr. Reiss by the national Arthritis Foundation that will support the group's continued efforts, researchers must demonstrate a unique understanding of a biomedical problem and a history of successful research projects on related topics.
Key to Dr. Reiss' success in receiving the "Innovative Research Grant" was her previous work at Winthrop in which she and her colleagues discovered that inflammation interferes with the handling of cholesterol by the body. This was a major step forward in understanding why people with rheumatoid arthritis and lupus have a higher rate of atherosclerosis (cholesterol build-up in the arteries), heart disease and heart attacks. Earlier work by Dr. Reiss and her colleagues found that elements of the patients' immune systems suppress their bodies' ability to clear the arteries of cholesterol in a normal fashion.
The new grant from the Arthritis Foundation will support continued research by Dr. Reiss, her co-investigator, Steven E. Carsons, M.D., Chief of Winthrop's Division of Rheumatology, Allergy and Immunology, and George K. Turi, M.D., Chief of Winthrop's Division of Immunohistopathology. Their work will continue to focus on identifying exactly which immune system components cause the failure to clear cholesterol, and via what molecular mechanisms they do so. In addition, Dr. Reiss' team will be exploring the ability of a substance found naturally in the body (adenosine) to restore the body's ability to clear cholesterol effectively.
Drs. Reiss and Carsons are co-editors of Proteins Involved in the Pathogenesis of Atherosclerosis, a book published in 2006 by Research Signpost. The book examines multiple aspects of recent developments in cardiovascular research.
