May 14, 2018

Novel therapies identified for patients with rheumatoid arthritis and potential for cardiovascular disease

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nagareddy streamPrabhakara Nagareddy, Ph.D., and Beatriz Hanoaka, M.D.Preclinical and early clinical research conducted by teams at the University of Alabama at Birmingham and in Australia suggests that patients with rheumatoid arthritis could lower their risk of cardiovascular disease through cholesterol-lowering therapies, according to research published in the European Heart Journal.

Rheumatoid arthritis is an auto-immune disease that affects 1 percent of the world’s population. These patients have a twofold higher risk of cardiovascular disease-related death compared to those with non-rheumatoid arthritis due to systematic inflammation. However, rheumatoid arthritis patients do not present traditional cardiovascular disease risk factors and symptoms, posing challenges for physicians in the treatment and management of both diseases.

“While cardiovascular disease is the number one killer of patients with rheumatoid arthritis, it’s hard for us to fully understand its genesis and poses major challenges in the cardiovascular management of these patients,” said Prabhakara Nagareddy, Ph.D., assistant professor in UAB’s Department of Nutrition Sciences and co-author of the study.

“With this research, we are looking to gather a better understanding of how systemic inflammation encourages plaque buildup that can lead to cardiovascular mortality and how we can treat it.”

The study’s objective was to determine if increased circulating myeloid cells were associated with atherosclerotic regression or altered progression in rheumatoid arthritis. Researchers found that increased cholesterol content in hematopoietic stem and progenitor cells in the bone marrow of mice with rheumatoid arthritis led to increased production of white blood cells, which in turn promoted atherosclerosis.

Researchers also demonstrated how the targeting of cellular cholesterol defects through reconstituted HDL, a super form of HDL that draws out cellular cholesterol, could limit atherosclerosis progression in mice with rheumatoid arthritis. While this would need to be tested in future clinical trials, this gives researchers hope that they are on the right track in developing effective detection methods and therapies to help this vulnerable subset of rheumatoid arthritis patients.

“If we find out that targeting cellular cholesterol defects through reconstituted HDL in mice with rheumatoid arthritis could limit atherosclerosis progression, it will ultimately help us get closer to limiting cardiovascular disease in these patients,” said Beatriz Hanoaka, M.D., assistant professor in UAB’s Division of Clinical Immunology and Rheumatology and co-author of the study. “These results are getting us closer to figuring out how to manage cardiovascular disease in patients with rheumatoid arthritis.”