S-nitrosylation: integrator of cardiovascular performance and oxygen delivery
Saptarsi M. Haldar, Jonathan S. Stamler
Saptarsi M. Haldar, Jonathan S. Stamler
Published January 2, 2013
Citation Information: J Clin Invest. 2013;123(1):101-110. https://doi.org/10.1172/JCI62854.
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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

Saptarsi M. Haldar, Jonathan S. Stamler

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Figure 3

SNO-based integration of oxygen utilization and homeostasis across organ systems.

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SNO-based integration of oxygen utilization and homeostasis across organ...
SNO-based signals exert coordinated effects across multiple organ systems to provide an integrated mechanism for sensing oxygen levels and executing molecular responses to hypoxic cues. The roles of SNOs in cardiac and skeletal muscle performance; respiratory cycle functions (vasodilator and vasoconstrictor function of Hb), including HVD and alveolar ventilation and perfusion matching (rbc NO permeability and trapping); the central ventilatory drive; and chronic adaptation to hypoxemia and anemia (HIF-1α signaling) are depicted. SNO-mediated activation of HIF-1α has been demonstrated in multiple tissues, including the kidney (127). Specific details shown in the kidney inset are derived, in part, from observations in the heart, brain, and other tissues. EPO, erythropoietin.