Smooth muscle cell CYB5R3 preserves cardiac and vascular function under chronic hypoxic stress.

ABSTRACT: Chronic hypoxia is a major driver of cardiovascular complications, including heart failure. The nitric oxide (NO) - soluble guanylyl cyclase (sGC) - cyclic guanosine monophosphate (cGMP) pathway is integral to vascular tone maintenance. Specifically, NO binds its receptor sGC within vascular smooth muscle cells (SMC) in its reduced heme (Fe²⁺) form to increase intracellular cGMP production, activate protein kinase G (PKG) signaling, and induce vessel relaxation. Under chronic hypoxia, oxidative stress drives oxidation of sGC heme (Fe²⁺→Fe³⁺), rendering it NO-insensitive. We previously showed that cytochrome b5 reductase 3 (CYB5R3) in SMC is a sGC reductase important for maintaining NO-dependent vasodilation and conferring resilience to systemic hypertension

SUBMITTER: Durgin BG 

PROVIDER: S-EPMC8766905 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature