Activated Platelets Induce Endothelial Cell Activation via an Interleukin-1β Pathway in Systemic Lupus Erythematosus.
Systemic lupus erythematosus (SLE) is associated with the premature development of cardiovascular disease. The platelet-endothelium interaction is important in the pathogenesis of cardiovascular disease. In this study, we investigated the platelet phenotype from patients with SLE and matched controls, and their effect on endothelial cells.



Platelet aggregability was measured in 54 SLE subjects off antiplatelet therapy (mean age 40.1±12.8 years; 82% female; 37% white) with age- and sex-matched controls. Platelets were coincubated with human umbilical vein endothelial cells (HUVECs) and changes to gene expression assessed by an RNA array and quantitative reverse transcription polymerase chain reaction. SLE disease activity index ranged from 0 to 22 (mean 5.1±3.9). Compared with controls, patients with SLE had significantly increased monocyte and leukocyte-platelet aggregation and platelet aggregation in response to submaximal agonist stimulation. An agnostic microarray of HUVECs cocultured with SLE platelets found a platelet-mediated effect on endothelial gene pathways involved in cell activation. Sera from SLE versus control subjects significantly increased (1) activation of control platelets; (2) platelet adhesion to HUVECs; (3) platelet-induced HUVEC gene expression of interleukin-8, and intercellular adhesion molecule 1; and (4) proinflammatory gene expression in HUVECs, mediated by interleukin-1β-dependent pathway. Incubation of SLE-activated platelets with an interleukin-1β-neutralizing antibody or HUVECs pretreated with interleukin-1 receptor antibodies attenuated the platelet-mediated activation of endothelial cells.



Platelet activity measurements and subsequent interleukin-1β-dependent activation of the endothelium are increased in subjects with SLE. Platelet-endothelial interactions may play a role in the pathogenesis of cardiovascular disease in patients with SLE.
From the Department of Medicine, Divisions of Cardiology (S.N., K.A.L., N.M.A., T.J.B., E.M., M.R., J.D.N., J.S.B.), Hematology (J.S.B.), and Rheumatology (R.C., J.N., S.R., J.P.B.), New York University School of Medicine, New York.
Sokha
S
Nhek
From the Department of Medicine, Divisions of Cardiology (S.N., K.A.L., N.M.A., T.J.B., E.M., M.R., J.D.N., J.S.B.), Hematology (J.S.B.), and Rheumatology (R.C., J.N., S.R., J.P.B.), New York University School of Medicine, New York.
Robert
R
Clancy
From the Department of Medicine, Divisions of Cardiology (S.N., K.A.L., N.M.A., T.J.B., E.M., M.R., J.D.N., J.S.B.), Hematology (J.S.B.), and Rheumatology (R.C., J.N., S.R., J.P.B.), New York University School of Medicine, New York.
Kristen A
KA
Lee
From the Department of Medicine, Divisions of Cardiology (S.N., K.A.L., N.M.A., T.J.B., E.M., M.R., J.D.N., J.S.B.), Hematology (J.S.B.), and Rheumatology (R.C., J.N., S.R., J.P.B.), New York University School of Medicine, New York.
Nicole M
NM
Allen
From the Department of Medicine, Divisions of Cardiology (S.N., K.A.L., N.M.A., T.J.B., E.M., M.R., J.D.N., J.S.B.), Hematology (J.S.B.), and Rheumatology (R.C., J.N., S.R., J.P.B.), New York University School of Medicine, New York.
Tessa J
TJ
Barrett
From the Department of Medicine, Divisions of Cardiology (S.N., K.A.L., N.M.A., T.J.B., E.M., M.R., J.D.N., J.S.B.), Hematology (J.S.B.), and Rheumatology (R.C., J.N., S.R., J.P.B.), New York University School of Medicine, New York.
Emanuela
E
Marcantoni
From the Department of Medicine, Divisions of Cardiology (S.N., K.A.L., N.M.A., T.J.B., E.M., M.R., J.D.N., J.S.B.), Hematology (J.S.B.), and Rheumatology (R.C., J.N., S.R., J.P.B.), New York University School of Medicine, New York.
Janet
J
Nwaukoni
From the Department of Medicine, Divisions of Cardiology (S.N., K.A.L., N.M.A., T.J.B., E.M., M.R., J.D.N., J.S.B.), Hematology (J.S.B.), and Rheumatology (R.C., J.N., S.R., J.P.B.), New York University School of Medicine, New York.
Sara
S
Rasmussen
From the Department of Medicine, Divisions of Cardiology (S.N., K.A.L., N.M.A., T.J.B., E.M., M.R., J.D.N., J.S.B.), Hematology (J.S.B.), and Rheumatology (R.C., J.N., S.R., J.P.B.), New York University School of Medicine, New York.
Maya
M
Rubin
From the Department of Medicine, Divisions of Cardiology (S.N., K.A.L., N.M.A., T.J.B., E.M., M.R., J.D.N., J.S.B.), Hematology (J.S.B.), and Rheumatology (R.C., J.N., S.R., J.P.B.), New York University School of Medicine, New York.
Jonathan D
JD
Newman
From the Department of Medicine, Divisions of Cardiology (S.N., K.A.L., N.M.A., T.J.B., E.M., M.R., J.D.N., J.S.B.), Hematology (J.S.B.), and Rheumatology (R.C., J.N., S.R., J.P.B.), New York University School of Medicine, New York.
Jill P
JP
Buyon
From the Department of Medicine, Divisions of Cardiology (S.N., K.A.L., N.M.A., T.J.B., E.M., M.R., J.D.N., J.S.B.), Hematology (J.S.B.), and Rheumatology (R.C., J.N., S.R., J.P.B.), New York University School of Medicine, New York. Jeffrey.berger@nyumc.org.
Jeffrey S
JS
Berger
D000328:Adult; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000097:blood* / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D015539:Platelet Activation / Q000187:drug effects; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D010979:Platelet Function Tests; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D055815:Young Adult
D057134:Antibodies, Neutralizing; C508585:IL1B protein, human; D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1
blood platelets; cardiovascular diseases; endothelial cells; interleukin-1; lupus erythematosus, systemic; platelet aggregation