The interplay of sleep deprivation, ferroptosis, and BACH1 in cardiovascular disease pathogenesis

Sleep deprivation (SD) can induce cardiac dysfunction, myocardial injury, and sudden death. The purpose of this study is to investigate whether the mechanism of sleep deprivation induced myocardial injury is related to abnormal expression of BACH1 and ferroptosis of myocardial cells.

Thirty-six male C57BL/6 J mice were used in the study. Twenty-four were exposed to SD through a modified multiple platform water method, while twelve served as controls. Cardiac function was assessed by small animal ultrasound super-resolution microimager and morphology by H&E staining. Ferroptosis model was established in H9c2 cardiomyocytes by Erastin. Biochemical assays measured key markers in serum and cell supernatants. TEM and flow cytometry evaluated mitochondrial changes and ROS levels. Western blot analyzed the expression of BACH1 and ferroptosis-related proteins.

Sleep deprivation caused increased heart rate (644 ± 30 bpm) and impaired cardiac function (EF 88.29 ± 3.97 %, FS 60.27 ± 2.70 %, LVIDd 3.14 ± 0.16 mm, LVIDs 1.30 ± 0.18 mm) in mice. It induced cardiomyocyte and mitochondrial damage, resulting in oxidative stress (MDA 7.16 ± 0.39 nmol/mg prot, GSH 33.88 ± 1.41 μg/mL, SOD 56.12 ± 1.44 U/mL, LDH 702.24 ± 33.48 U/L) and elevated CK levels (43.78 ± 2.30 U/mL). The expression of ANP, BACH1, and ferroptosis-related proteins (TFRC, SLC7A11, GPX4, NQO1, and HO-1) was altered. We observed aberrant oxidative stress indicators and expression of BACH1 and ferroptosis-related proteins in an Erastin-induced H9c2 cardiomyocytes model.

Sleep deprivation promotes BACH1 through ferroptosis and leads to myocardial injury, thereby revealing potential therapeutic targets for CVDs.