Lysine lactylation analysis of proteins in the heart of the Kawasaki disease mouse model.

Abstract

Introduction: Kawasaki disease (KD) is a medium-vessel vasculitis predominantly affecting children under 5 years of age and may involve the coronary arteries.

Methods: A mouse KD model was induced by Candida albicans cell wall extracts (CAWS), cardiac tissues were analyzed through integrated lactylomic and proteomic profiling. The lysine lactylation (Kla) results were normalized to the proteomic data.

Results: Elevated serum lactate and lactate dehydrogenase (LDH) levels were observed in KD patients. Given lactate's role as a substrate for Kla, this study investigated Kla modifications in KD. Proteomic analysis identified 150 upregulated proteins and 18 downregulated proteins, with 38.1% located in the cytoplasm and significant enrichment in immune-related pathways. After normalization, 41 sites in 37 proteins were found to be upregulated in the Kla data, with no downregulated sites. Approximately 67.57% of the altered proteins were localized in the mitochondria. Bioinformatics analysis indicated alterations in aerobic respiration, energy production and conversion, and key immune- and metabolism-related pathways.

Discussion: This study enhances the understanding of Kla modifications in the development of KD and may inform targeted therapies for its prevention and improved prognosis.