Affiliation:
1. Department of Pediatrics University of California, San Diego La Jolla CA
2. Department of Biomedical Informatics University of California, San Diego La Jolla CA
3. Department of Medicine University of California, San Diego La Jolla CA
4. Rady Children’s Hospital San Diego CA
Abstract
Background
Damage to the coronary arteries during the acute phase of Kawasaki disease (KD) is linked to inflammatory cell infiltration, myointimal proliferation, and endothelial cell (EC) dysfunction. To understand the response of ECs to KD treatment, we studied the genome‐wide transcriptional changes in cultured ECs incubated with KD sera before and after treatment with or without atorvastatin.
Methods and Results
RNA sequencing of human umbilical vein ECs incubated with pooled sera from patients with acute KD before or after treatment with intravenous immunoglobulin and infliximab revealed differentially expressed genes in interleukin‐1, tumor necrosis factor‐α, and inflammatory cell recruitment pathways. Subacute sera pooled from patients treated with intravenous immunoglobulin, infliximab, and atorvastatin uniquely induced expression of
NOS3
, Kruppel like factor (
KLF2
, and
KLF4
(promotes EC homeostasis and angiogenesis) and ZFP36 ring finger protein (ZFP36) and suppressor of cytokine signaling 3 (SOCS3) (suppresses inflammation), and suppressed expression of
TGFB2
and
DKK1
(induces endothelial‐mesenchymal transition) and sphingosine kinase 1 (SPHK1) and C‐X‐C motif chemokine ligand 8 (CXCL8) (induces inflammation).
Conclusions
These results suggest that atorvastatin treatment of patients with acute KD may improve EC health, reduce mediators of inflammation produced by ECs, and block KD‐induced myofibroblast proliferation.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
2 articles.
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