Conditional deletion of Vhl in cardiac vascular progenitors induces coronary artery dilation, vascular remodeling, thrombosis, and inflammation, recapitulating severe cardiac manifestations of Kawasaki disease (KD).
HIF2 activation is identified as the pivotal driver mediating these pathological changes, as simultaneous Hif2a deletion rescues vascular abnormalities in the mouse model.
Transcriptomic and histologic analyses reveal disrupted extracellular matrix organization, calcification, and perivascular fibrosis, underpinning compromised vascular stability.
Human cardiac samples from fatal KD cases show intense HIF2 expression in coronary lesions and inflammatory infiltrates, validating clinical relevance of the hypoxia pathway in KD pathogenesis.
