title: S-nitrosylation: integrator of cardiovascular performance and oxygen delivery.
abstract: Delivery of oxygen to tissues is the primary function of the cardiovascular system. NO, a gasotransmitter that signals predominantly through protein S-nitrosylation to form S-nitrosothiols (SNOs) in target proteins, operates coordinately with oxygen in mammalian cellular systems. From this perspective, SNO-based signaling may have evolved as a major transducer of the cellular oxygen-sensing machinery that underlies global cardiovascular function. Here we review mechanisms that regulate S-nitrosylation in the context of its essential role in "systems-level" control of oxygen sensing, delivery, and utilization in the cardiovascular system, and we highlight examples of aberrant S-nitrosylation that may lead to altered oxygen homeostasis in cardiovascular diseases. Thus, through a bird's-eye view of S-nitrosylation in the cardiovascular system, we provide a conceptual framework that may be broadly applicable to the functioning of other cellular systems and physiological processes and that illuminates new therapeutic promise in cardiovascular medicine.
authors.affiliation: Department of Medicine and Cardiovascular Division, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, Ohio, USA. saptarsi.haldar@case.edu
authors.forename: Saptarsi M
authors.initials: SM
authors.lastname: Haldar
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Stamler
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*
chemical_list: D009569:Nitric Oxide; D010100:Oxygen