Mariana J. Kaplan, MD

University of Michigan, Ann Arbor, MI

2002 Cardiovascular System
2002 Biomarkers

Young premenopausal women with lupus are significantly more at risk of heart disease and stroke than healthy young females. In fact, premature heart disease is the third most common cause of death in these patients, following complications of kidney disease and infection.

With Lupus Research Institute funding, Dr. Kaplan set out to investigate the mechanisms by which blood vessels are damaged in women with lupus and lead to premature vascular disease.

She discovered that some people with lupus appear to get premature atherosclerotic changes due to the rapid death and slow replacement of endothelial cells. These cells, which line the blood vessels and cavities of the heart, normally keep plaques and clots from forming.

“We found that the lupus patients had abnormal vascular function that was impaired to the same extent seen in the heart disease patients – despite the fact that the lupus patients were approximately half the age,” she explained.

Citing research that points to a role for programmed cell death (called “apoptosis”) of white blood cells within tissues (macrophages) in inducing autoimmunity, Dr. Kaplan aims to find out more about this process so that it can be halted.

Dr. Kaplan has been published widely and also shared these and other results from her LRI-funded work, such as the discovery that poor vascular function in people with lupus is associated with increased levels of a protein that regulates blood clotting, at several international meetings.

Along with the six investigators now working on the topic that the LRI funded her for in 2002, Dr. Kaplan is hopeful that her discoveries will lead to a biomarker to identify people with lupus at risk of cardiovascular disease. She envisions designing therapies to prevent endothelial cell damage and thereby slash the risk for premature atherosclerosis.

Select publications:

Accelerated macrophage apoptosis induces autoantibody formation and organ damage in systemic lupus erythematosus. Denny MF, Chandaroy P, Killen PD, Caricchio R, Lewis EE, Richardson BC, Lee KD, Gavalchin J, Kaplan MJ. J Immunol. 2006 Feb 15;176(4):2095-104.

Plasminogen activator inhibitor-1 is associated with impaired endothelial function in women with systemic lupus erythematosus. Somers EC, Marder W, Kaplan MJ, Brook RD, McCune WJ. Ann N Y. Acad Sci. 2005 1051:271-80.

Apoptosis in systemic lupus erythematosus. Kaplan MJ. Clin Immunol. 2004 Sep; 112(3):210-8.

Endothelial cell apoptosis in systemic lupus erythematosus: a common pathway for abnormal vascular function and thrombosis propensity. Rajagopalan S, Somers EC, Brook RD, Kehrer C, Pfenninger D, Lewis E, Chakrabarti A, Richardson BC, Shelden E, McCune WJ, Kaplan MJ. Blood. 2004 103(10):3677-83.

Ongoing funding:

In 2005, Kaplan won $200,000 from the Alliance for Lupus Research grant to further research the findings she made through her LRI grant. And in 2009, she received a $1.5 million grant from the NIH’s National Heart, Lung, and Blood Institute to continue the promising work on mechanisms of premature vascular disease in lupus.

Rev. July 2010

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