Rajagopalan and Kaplan, along with a team of U-M colleagues, suspected something must be damaging the endothelial cell layer in order to cause cardiovascular disease in women with no other risk factors besides lupus. They set out to determine if they could see these apoptotic endothelial cells in the blood, and correlate them to both vascular function and the flaring up of lupus symptoms.
"We hypothesized that rapid apoptosis could exist at the level of the endothelial cells, that they might commit suicide and thereby affect vascular function," says Rajagopalan.
Apoptosis is a normal process by which cells self-destruct at the end of their useful lives. Endothelial cells routinely die, and are taken away by the body's "garbage truck" cells. But previous research has shown that in lupus, there's an increased pace of cell suicide in major organs and a decreased clearance of those dead cells by the immune system.
For the new study, the U-M researchers tested blood for the presence of a type of endothelial cell called CD146, combined with a test for the apoptosis-related protein annexin V. They found that lupus patients had about seven times the levels of endothelial cells and annexin V seen in the normal and heart-diseased patients. "It's as if more garbage was being generated than could be cleaned up by the body's normal means, so it piled up in the blood," says Rajagopalan.
The researchers also measured all the study participants' vascular health by monitoring blood flow in the arm using techniques often used for people with vascular disease: brachial-artery-flow-mediated dilation and nitroglycerin-mediated dilation. Both the lupus patients and coronary artery disease patients had abnormal flow-mediated dilation, while normal control subjects did not.