Accumulation of angiotensin II can also activate the nuclear factor-kappa (NF-κB)-signaling pathway and the interleuking-6 (IL-6) pathway.[30] The activation of the NF-κB pathway has an important role in the pathogenesis of inflammatory diseases (Fig. 15).[31,32] This is accompanied by an age-related decline in the ACE2 receptors and can lead to the proinflammatory end-organ tissue damage and wide systemic endothelial dysfunction and microangiopathic abnormalities seen in COVID-19.[33,34] ACE2 receptor overexpression has been established to play a protective role in ischemic stroke.[35,36]. This evidence concerns the gene NFKB1 and ischemic stroke.