Delivery of β-Klotho to the heart using ultrasound-targeted microbubble destruction (UTMD) technology enhances sensitivity to FGF21 by up-regulating Nrf2 target proteins such as heme oxygenase 1 (HO-1), NAD(P) H quinone dehydrogenase 1 (NQO1), glutamate-cysteine ligase modifier subunit (GCLM), effectively alleviating post-infarction-induced myocardial oxidative stress and mitochondrial injury, thereby significantly ameliorating cardiac insufficiency’ adverse remodeling (77). Here, HMOX1 is linked to heart failure.