Abstract
BackgroundKawasaki disease (KD) is an acute febrile vasculitis in childhood, which is the leading cause of acquired heart disease in children. If untreated, KD can result in coronary aneurysms in 25% of patients, and even under intravenous immunoglobulin (IVIG) treatment, 10–20% of children will have IVIG resistance and increased risk of developing coronary arteritis complication. Additional therapies should be explored to decrease the incidence of coronary artery lesions and improve the prognosis in KD. Autophagy has been reported to play a critical role in a variety of heart diseases. Resveratrol (RSV) confers cardio protection during ischemia and reperfusion in rats via activation of autophagy. Serum TNF-alpha levels are elevated in KD, which might activate the endothelial cells to express intercellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1(VCAM-1), inducible nitric oxide synthase (iNOS) and IL-1β.MethodsHuman coronary arterial endothelial cells (HCAECs) were either untreated or treated by TNF-α 10 ng/ml for 2 h in the presence or absence of RSV or autophagy-related protein 16-like 1 (Atg16L1) siRNA. Total RNA was analyzed by real-time quantitative PCR for ICAM-1, VCAM-1, iNOS and IL-1β mRNA expressions. The involvement of autophagy proteins was investigated by Western blot.ResultsPretreatment with resveratrol significantly inhibited TNF-α-induced ICAM-1, iNOS and IL-1β mRNA expression in HCAECs. Western blot revealed the enhanced autophagy proteins LC3B and Atg16L1 expression by RSV. The suppressive effects of RSV were obviously counteracted by Atg16L1 siRNA.ConclusionsWe demonstrated RSV had anti-inflammatory effects on HCAECs via induction of autophagy. Our results suggest that resveratrol may modulate the inflammatory response of coronary artery in KD and explore the role of autophagy in the pathogenesis and alternative therapy of coronary arterial lesions in KD.
Highlights
Kawasaki disease (KD) is an acute febrile vasculitis in childhood, which is the leading cause of acquired heart disease in children
We examined if the induction of autophagy by RSV played an anti-inflammatory effects on TNF-alphainduced expression of adhesion molecule (VCAM-1 and intercellular adhesion molecule-1 (ICAM-1)) and production of cytokine (interleukin (IL)-1beta and inducible nitric oxide synthase (iNOS)) in Human coronary arterial endothelial cells (HCAECs)
Inhibitory effects of RSV on TNF-α-induced ICAM-1 mRNA expression TNF-α is necessary for induction of coronary artery inflammation and aneurysm formation in an animal model of KD [23]; we used TNF-α to treat human coronary endothelial cells as an in vitro model for KD
Summary
Kawasaki disease (KD) is an acute febrile vasculitis in childhood, which is the leading cause of acquired heart disease in children. Resveratrol (RSV) confers cardio protection during ischemia and reperfusion in rats via activation of autophagy. Kawasaki disease (KD) is the leading cause of acquired heart disease in children in the developed world [1]. Patients who suffer coronary artery damage may develop aneurysms and are at risk of clinical cardiovascular events, and even sudden death [2, 3]. Resveratrol (RSV), a red wine-derived polyphenolic compound, has been shown to have significant effects in various disease models such as cardioprotection in ischemic heart, diabetes, chemoprevention of cancers, etc. RSV confers cardioprotection during ischemia and reperfusion in rats via activation of autophagy. Control of autophagy by RSV may represent a potential target to treat or prevent development of coronary arterial lesions (CAL) in KD
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