RYR2 and endothelial dysfunction: Key implicated pathways include dysregulated calcium handling (CaMKII/RyR2), inflammation (NLRP3), fibrosis, and endothelial dysfunction (VEGF/PI3K-NO) (Kudinov and Darbar, 2020; N. Liu et al., 2013; McMullen et al., 2014; Pandey et al., 2018; Ping et al., 2017).