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Transcript
1546
poster
Cat: Pharmacologic modulation of vascular-endothelial funciton
ANTI-INFLAMMATORY EFFECT OF RESVERATROL IN HUMAN
CORONARY ARTERIAL ENDOTHELIAL CELLS VIA AUTOPHAGY:
IMPLICATION FOR THE TREATMENT OF KAWASAKI DISEASE
F.C. Huang1,2, H.C. Kuo2,3, H.R Yu2,3
1. Division of Gastroenterology and Hepatology; Department of Pediatrics, Kaohsiung Chang
Gung Memorial Hospital, Taiwan
2. Chang Gung University College of Medicine
3. Division of Allergy, Immunology and Rheumatology; Department of Pediatrics, Kaohsiung
Chang Gung Memorial Hospital, Taiwan
Kawasaki disease (KD) is an acute febrile vasculitis of childhood and is the leading cause
of acquired heart disease in children in the developed world. If untreated, KD can result in
coronary aneurysms in 25% of patients, who are at risk of myocardial infarction, sudden
death, and congestive heart failure. Despite the success, 10-20% of children will have
persistent or recrudescent fever after their first infusion of IVIG. These patients are at
increased risk of developing coronary artery abnormalities. Additional therapies should be
explored to decrease the incidence of coronary arteritis complication and improve the
prognosis in Kawasaki disease. Induced autophagy with resveratrol confers
cardioprotection during ischemia and reperfusion in rats.
KD is associated with elevated production of inflammatory cytokines, causing damage to
the coronary arteries. Serum TNF-alpha levels are elevated in KD, which was supposed to
activate the endothelial cells. As a result, adhesion molecules such as intercellular adhesion
molecule-1 (ICAM-1) and vascular cellular adhesion molecule-1(VCAM-1) are expressed
in the endothelial cells, and leucocytes adhere firmly to endothelial cells. The leucocytes
then damage the endothelial cells and smooth muscle cells and cause vasculitis.
In this study, we examined the anti-inflammatory effects of resveratrol on
TNF-alpha-induced adhesion molecule expression (VCAM-1 and ICAM-1) and cytokine
production (interleukin (IL)-1beta, IL-6 and IL-8) in HCAECs. Pretreatment with
resveratrol significantly inhibited TNF-alpha-induced adhesion molecules and cytokines
production in HCAECs via the activation of autophagy. Our results suggest that adjunctive
resveratrol therapy may modulate the inflammatory response during KD vasculitis and
explore the role of autophagy in the pathogenesis of the complication and the promising
therapy.