SQSTM1 and heart failure: Indeed, pVHL loss has been shown to result in cardiac inflammation, apoptotic cell death, and pathological hypertrophy through NF-κB (nuclear factor-κB) activation, and NF-κB inhibition is protective in the setting of heart failure.42,43 Whole-body Depp1 loss did not reduce NF-κB activation in hearts lacking pVHL, as measured by NF-κB p62 S536 and IKKαβS176/S177 phosphorylation in immunoblot assays (Figure S19A).