title: Endothelial cell apoptosis in systemic lupus erythematosus: a common pathway for abnormal vascular function and thrombosis propensity.
abstract: Women with systemic lupus erythematosus (SLE) are at risk for premature atherothrombosis independent of Framingham risk factors. We investigated whether endothelial cell (EC) apoptosis predicts abnormal vasomotor tone and contributes to circulating tissue factor (TF) levels in this disease. Brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated dilation were determined in women with SLE, healthy control subjects, 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 [CD146(AnnV+)]) and immunofluorescent microscopy. Plasma TF was measured by enzyme-linked immunosorbent assay (ELISA). Compared with healthy control and CAD subjects, patients with SLE had higher numbers of circulating CD146(AnnV+) cells (10 +/- 3, 18 +/- 5, and 89 +/- 32 cells/mL, respectively, mean +/- SEM; P <.01). Increased CD146(AnnV+) cells correlated strongly with abnormal vascular function (P =.037). After adjusting for known predictors of endothelial function, CD146(AnnV+) was the only variable that predicted FMD (beta = -4.5, P <.001). Increased CD146(AnnV+) was strongly associated with elevated levels of circulating TF (r =.46, P =.002). Circulating apoptotic ECs are elevated in young women 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 atherothrombosis in SLE.
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109-0680, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
authors.forename: Emily C
authors.initials: EC
authors.lastname: Somers
authors.forename: Robert D
authors.initials: RD
authors.lastname: Brook
authors.forename: Christine
authors.initials: C
authors.lastname: Kehrer
authors.forename: Dana
authors.initials: D
authors.lastname: Pfenninger
authors.forename: Emily
authors.initials: E
authors.lastname: Lewis
authors.forename: Anjan
authors.initials: A
authors.lastname: Chakrabarti
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Richardson
authors.forename: Eric
authors.initials: E
authors.lastname: Shelden
authors.forename: W Joseph
authors.initials: WJ
authors.lastname: McCune
authors.forename: Mariana J
authors.initials: MJ
authors.lastname: Kaplan
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D001775:Blood Circulation; D016022:Case-Control Studies; D042783:Endothelial Cells / Q000473:pathology*; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013925:Thromboplastin / Q000032:analysis; D013927:Thrombosis / Q000209:etiology; D014652:Vascular Diseases / Q000209:etiology*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D013925:Thromboplastin