Increased oxidant production and DNA damage are key early molecular events in PKP2-deficient ARVC, suggesting that therapies limiting oxidant formation could be a potential early intervention.
Loss of nuclear envelope integrity and subsequent DNA damage is a key substrate in the molecular pathology of ARVC. We show transcriptional downregulation of proteins of the electron transcript chain as an early event in the molecular pathophysiology of the disease (before loss of left ventricular ejection fraction 2.- and H2O2). We propose therapies that limit oxidant formation as a possible intervention to restrict DNA damage in ARVC.
Pérez-Hernández et al. (2022) studied this question.