Background: Hypertrophic cardiomyopathy (HCM) is characterized by myocyte hypertrophy and fibrosis. Studies in two mouse models (R92W-TnT/R403Q-MyHC) at early HCM stage revealed upregulation of endothelin (ET1) signaling in both mutants, but TGFβ signaling only in TnT mutants. Dysregulation of miR-29 expression has been implicated in cardiac fibrosis. But it is unknown whether expression of miR-29a/b/c and profibrotic genes is commonly regulated in mouse and human HCM. Conclusions: Our in vitro studies suggest that activation of ET1 signaling in cardiac myocytes increases reactive oxygen species and stimulates TGFβ secretion, which downregulates miR-29a and increases collagen in fibroblasts, thus contributing to fibrosis. Our gene expression studies in mouse and human HCM reveal allele-specific differences in miR-29 family/profibrotic gene expression in mouse HCM, and activation of anti-hypertrophic/anti-fibrotic genes and pathways in human HCM.

A 58-year-old Caucasian male developed generalized weakness, bilateral upper and lower extremity arthralgias, left pedal edema, and a new rash over two weeks after receiving one dose of dupilumab for chronic sinusitis. He was found to be positive for perinuclear anti-neutrophil cytoplasmic antibodies and myeloperoxidase, with evidence of interstitial lung disease on CT imaging. A skin biopsy showed eosinophilic vasculitis and a kidney biopsy showed pauci-immune glomerulonephritis. He was diagnosed with eosinophilic granulomatosis with polyangiitis due to dupilumab exposure.

No abstract

No abstract

No abstract