Familial HCM is an autosomal dominant disease of the cardiac sarcomere, mainly due to mutations in the MYH-7 protein, which results in abnormal thickening of the left ventricular myocardium and is associated with elevated circulating levels of the biomarker NT-proBNP in patients. HCM was induced by Endothelin-1 (ET-1, a potent pro-hypertrophic peptide produced by endothelial and smooth muscle cells) in bioreactor-derived cardiomyocytes. Overnight exposure of bioreactor-derived iPSC-CMs to ET-1 results in production of BNP as measured by immunofluorescence microscopy.
(A) Control or ET-1 treated cardiomyocytes were stained for BNP (green) and nuclei (blue). (B) Quantification of high content images showing total nuclear area (left) or BNP expression (right) in the presence or absence of ET-1. (C) ET-1 induced NT-proBNP secretion, measured by AlphaLISA, was rescued by treatment with Verapamil.