The Murine Model of Kawasaki Disease Vasculitis
Intestinal Permeability and Gut Microbiome in Kawasaki Disease
Spatial Transcriptomics and Single-Cell Transcriptional Profiling of Murine Abdominal Aorta Aneurysms
A better understanding and characterization of the cellulome and the molecular networks at steady-state and in cardiovascular lesions that develop during murine KD is essential to understand this pathology and to formulate more precise therapeutic strategies. The Noval Rivas Laboratory is using novel high-throughput sequencing techniques, such as single-cell RNA sequencing and spatial transcriptomics, to characterize the immune cell infiltrations associated with the development of cardiovascular lesions during murine KD. Those novel techniques have the capacities and advantage to assess gene expression in individual cells with high resolution and will highlight cell-type-specific transcriptional networks that underpin disease development.
Autophagy and Mitophagy in Murine Kawasaki Disease Vasculitis
The NLRP3 inflammasome activation and consecutive interleukin-1β (IL-1β) maturation and secretion play a crucial role for the development of both human and murine KD vasculitis. NLRP3 inflammasome can be activated by damaged mitochondrial DNA (mtDNA), which is released after reactive oxidative stress injury and functions as damage-associated molecular patterns. Damaged mitochondria and high levels of mtDNA in the cytosol are recognized by the autophagy machinery, leading to their degradation through the autolysosome. Therefore, autophagy and mitophagy may play an important role in the prevention of cardiovascular lesions in KD vasculitis by diminishing/inhibiting NLRP3 activation, its consecutive IL-1β secretion and the resulting tissue damages. The exact role of autophagy and mitophagy in this context still remains unclear and the lab is currently investigating this pathway.