2003/2004 Biomarkers, Cardiovascular System, Human Lupus Biology
2010 Human Lupus Biology
In 2003/2004, Dr. Clancy won LRI funding to establish whether early changes in the characteristics of circulating endothelial cells predict the development of atherosclerosis in people with lupus.
Endothelial cells are likely participants in the inflammation that leads to tissue damage and subsequent atherosclerotic changes that can cause heart attacks and strokes in people with lupus. They’re activated by immune stimuli likely present during a lupus flare.
His team went on to confirm that circulating endothelial cells are indeed elevated in people with lupus and accelerated atherosclerosis. Endothelial disorders are “an underdeveloped area for drug development and our work will put a spotlight on it,” Dr. Clancy said.
“I recently entered into a consortium on an application (with Dr. Betty Tsao, PI) to participate in a multicentered project on the theme of SLE, vasculopathy and biomarkers of atherosclerosis,” reported Dr. Clancy in 2010.
In 2011, Dr. Clancy won another LRI Novel Research Grant.
Sometimes lupus affects the function of cells in “good” blood vessels responsible for performing such jobs as regulating blood pressure, keeping water distributed properly in the body, and providing instructions to “white blood cells” to keep them healthy.
With his 2011 LRI funding, Dr. Clancy aims to refute the notion that the “bad” things that happen to blood vessels are irrevocable. Specifically, a protein called “active protein C” which is generated by good blood vessels is central to normal function. People with lupus tend to have low levels of “active protein C,” which in turn causes an imbalance that can result in damaging inflammation to blood vessels throughout the body.
A rationale approach: “infuse” a replacement “active protein C” to restore levels. But blood clotting might occur. Alternatively, Dr. Clancy will use an “engineered” active protein C which benefits blood vessels cells while avoiding the adverse blood clotting effect.
By exploring the pathways through which low levels of this protein cause inflammation, Dr. Clancy will test whether infusing mice with the protein might actually restore healthy blood vessels—preventing worsening of lupus kidney disease in particular.
Association of plasma soluble E-selectin and adiponectin with carotid plaque in patients with systemic lupus erythematosus. Reynolds HR, Buyon J, Kim M, Rivera TL, Izmirly P, Tunick P, Clancy RM. Atherosclerosis. 2010 Jun;210(2):569-74.
Shedding of endothelial protein C receptor contributes to vasculopathy and renal injury in lupus: In vivo and in vitro evidence. Sesin CA, Yin X, Esmon CT, Buyon JP, Clancy RM. Kidney Int. 2005 Jul; 68(1):110-20.
Based on discoveries made with his 2003/2004 LRI grant, Dr. Clancy subsequently won a $1 million grant from the NIH to further expand on this research.
Rev. March 2011