Frontiers in immunology · 2026
Itaconate ameliorates cardiovascular inflammation in a mouse model of Kawasaki disease vasculitis - brief report.
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Lee Youngho, Namba Takahiro, Atici Asli E, Aubuchon Emily, Lane Malcolm E, Ross Benjamin L, Noval Rivas Magali, Arditi Moshe
Аннотация
BACKGROUND: Kawasaki disease (KD), a systemic vasculitis and the leading cause of acquired heart disease in children, stems from an uncontrolled inflammatory response that fails to resolve in up to 20% of IVIG-treated patients. This treatment resistance increases the risk of cardiovascular complications and highlights the need for more targeted therapeutics.
METHODS: We used the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis to investigate the therapeutic potential of itaconate, an anti-inflammatory metabolite, in the pathogenesis of KD. The expression of aconitate decarboxylase 1 (Acod1), which encodes the mitochondrial enzyme that produces itaconate, was assessed in both samples from KD patients and vascular tissues of LCWE-injected mice. LCWE-injected mice were treated with itaconate, and the severity of LCWE-induced KD vasculitis was evaluated.
RESULTS: LCWE injection led to the development of cardiovascular lesions, specifically aortitis, coronary arteritis, and abdominal aorta dilatation. Expression of ACOD1 was upregulated in KD patients during the acute phase of the disease and in cardiovascular lesions of LCWE-injected mice. Treatment with itaconate significantly reduced the development of LCWE-induced cardiovascular lesions. Mechanistically, exogenous itaconate suppressed NLRP3 inflammasome activation in LCWE-induced cardiovascular lesions and decreased IL-1β secretion.
CONCLUSIONS: Itaconate treatment provides cardiovascular protection in an experimental mouse model of KD vasculitis by decreasing NLRP3 inflammasome activation and reducing vascular inflammation. Itaconate may be a promising therapeutic agent for patients with KD.
METHODS: We used the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis to investigate the therapeutic potential of itaconate, an anti-inflammatory metabolite, in the pathogenesis of KD. The expression of aconitate decarboxylase 1 (Acod1), which encodes the mitochondrial enzyme that produces itaconate, was assessed in both samples from KD patients and vascular tissues of LCWE-injected mice. LCWE-injected mice were treated with itaconate, and the severity of LCWE-induced KD vasculitis was evaluated.
RESULTS: LCWE injection led to the development of cardiovascular lesions, specifically aortitis, coronary arteritis, and abdominal aorta dilatation. Expression of ACOD1 was upregulated in KD patients during the acute phase of the disease and in cardiovascular lesions of LCWE-injected mice. Treatment with itaconate significantly reduced the development of LCWE-induced cardiovascular lesions. Mechanistically, exogenous itaconate suppressed NLRP3 inflammasome activation in LCWE-induced cardiovascular lesions and decreased IL-1β secretion.
CONCLUSIONS: Itaconate treatment provides cardiovascular protection in an experimental mouse model of KD vasculitis by decreasing NLRP3 inflammasome activation and reducing vascular inflammation. Itaconate may be a promising therapeutic agent for patients with KD.