Sigmar1 has a significant therapeutic potential to treat the cardiovascular disease as reflected by two Sigmar1 ligands already in clinical trials: cutamesine (SA4503) for ischemic stroke (Phase II) (Urfer et al., 2014) and sertraline for depression in patients with heart failure (SADHART-CHF) (Serebruany et al., 2003, 2005; Swenson et al., 2003; Glassman et al., 2006; Jiang et al., 2008, 2011; O’Connor et al., 2010; Xiong et al., 2012, 2015). Here, SIGMAR1 is linked to heart failure.