Acetoacetate increases expression of intercellular adhesion molecule-1 (ICAM-1) in human brain microvascular endothelial cells.
It has been hypothesized that ketone bodies cause activation of brain endothelial cells and that this is a factor in the intracerebral crises of diabetic ketoacidosis (DKA). In this study we used cultured human brain microvascular endothelial cells (HBMEC) to investigate the effect of beta hydroxybutyrate (BOHB) and acetoacetate (AcAc) on the expression of the adhesion molecule, intercellular adhesion molecule-1 (ICAM-1). Increasing concentrations of AcAc, but not BOHB, caused a significant upregulation of ICAM-1 in comparison to unstimulated cells. Glucose concentrations of 10 and 30 mM, but not 50 mM, also resulted in increased expression of ICAM-1. These results support the hypothesis that activation of HBMEC is involved in the acute complications of DKA, and that ketone bodies and hyperglycemia are factors in the perturbed membrane function.
Hoffman
William H
WH
Section of Pediatric Endocrinology, Department of Pediatrics, BG-2000H, Medical College of Georgia, Augusta, GA 30912, USA.
Cheng
Charles
C
Passmore
Gregory G
GG
Carroll
James E
JE
Hess
David
D
D020155:3-Hydroxybutyric Acid / Q000008:administration & dosage / Q000494:pharmacology; D000090:Acetoacetates / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D016883:Diabetic Ketoacidosis / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects
D000090:Acetoacetates; D018799:Intercellular Adhesion Molecule-1; C016635:acetoacetic acid; D005947:Glucose; D020155:3-Hydroxybutyric Acid