Nolan T Carew, Heidi M Schmidt, Shuai Yuan, Joseph C Galley, Robert Hall, Helene M Altmann, Scott A Hahn, Megan P Miller, Katherine C Wood, Bethann Gabris, Margaret C Stapleton, Sean Hartwick, Marco Fazzari, Yijen L Wu, Mohamed Trebak, Brett A Kaufman, Charles F McTiernan, Francisco J Schopfer, Placido Navas, Patrick H Thibodeau, Dennis M McNamara, Guy Salama, Adam C Straub
Sudden cardiac death (SCD) in patients with heart failure (HF) is allied with an imbalance in reduction and oxidation (redox) signaling in cardiomyocytes; however, the basic pathways and mechanisms governing redox homeostasis in cardiomyocytes are not fully understood. Here, we show that cytochrome b5 reductase 3 (CYB5R3), an enzyme known to regulate redox signaling in erythrocytes and vascular cells, is essential for cardiomyocyte function. Using a conditional cardiomyocyte-specific CYB5R3-knockout mouse, we discovered that deletion of CYB5R3 in male, but not female, adult cardiomyocytes causes cardiac hypertrophy, bradycardia, and SCD...
September 15, 2022: Journal of Clinical Investigation