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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3677-3683.
Prepublished online as a Blood First Edition Paper on January 15, 2004; DOI 10.1182/blood-2003-09-3198.


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Submitted September 17, 2003
Accepted January 6, 2004

Endothelial Cell Apoptosis in Systemic Lupus Erythematosus: A Common Pathway for Abnormal Vascular Function and Thrombosis Propensity

Sanjay Rajagopalan, Emily C Somers, Robert D Brook, Christine Kehrer, Dana Pfenninger, Emily Lewis, Anjan Chakrabarti, Bruce C Richardson, Eric Shelden, William J McCune, and Mariana J Kaplan*

Internal Medicine, University of Michigan, Ann Arbor, MI, USA
Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, USA

* Corresponding author; email: makaplan{at}umich.edu.

Women with systemic lupus erythematosus (SLE) are at risk for premature athero-thrombosis independent of Framingham risk factors. We investigated if endothelial cell (EC) apoptosis predicts abnormal vasomotor tone and contributes to circulating tissue factor (TF) levels in this disease. Brachial artery flow mediated (FMD) and nitroglycerin mediated dilation were determined in women with SLE, healthy controls and subjects with coronary artery disease (CAD) (n=43/group). Quantification of circulating apoptotic ECs was performed by flow cytometry [CD146+ cells that stained for Annexin V (CD146AnnV+)] and immunofluorescent microscopy. Plasma TF was measured by ELISA. Compared to healthy controls or CAD, SLE patients had higher numbers of circulating CD146AnnV+ (10 ±3, 18 ±5, and 89 ±32 cells/ml, respectively, mean+ SEM; p<0.01). Increased CD146AnnV+ cells correlated strongly with abnormal vascular function (p = 0.037). After adjusting for known predictors of endothelial function, CD146AnnV+ was the only variable that predicted FMD ({beta}= -4.5, p<0.001). Increased CD146AnnV+ was strongly associated with elevated levels of circulating TF (r= 0.46, p=0.002). Circulating apoptotic ECs are elevated in young females with SLE and strongly correlate with markedly abnormal vascular function and elevated TF levels. Heightened endothelial apoptosis may represent an important mechanism for development of athero-thrombosis in SLE.


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Endothelial apoptosis: the missing link between atherosclerosis and SLE?
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