TNFα activates Orai-Ca2+ influx after binding to TNFR2 and potential production of AA metabolites via the lipoxygenase pathway in hypertrophied cardiomyocytes from rats with AAB-induced EACH. (A) Schematic representation of the protocol where rats with AAB-induced EACH for 28 days were subjected to echographic analyses. (B–E) Hypertrophied cardiomyocytes isolated from AAB rats were loaded with Fura2 before measurement of voltage- and store-independent Ca2+ influx. TNFα activates Ca2+ entry (B) in a manner sensitive to Orai inhibitor YM58483 (C), neutralizing TNFR2-Ab (D) or lipoxygenase inhibitor NDGA (E). Number of cells analyzed and number of cell isolations (rats) as indicated, mean ± SEM of cells, Wilcoxon matched-paired tests to examine if the mean of the 2nd rate differs from the 1st one, arbitrarily set as 1 (B,D,E) or 2.2 (C) ****p < 0.0001.