Signaling from red blood cells can induce vasodilation in response to local decreases in oxygenation. This signaling critically depends on the formation of S-nitrosohemoglobin via S-nitrosylation at residue Cys93 on the β-chain of hemoglobin. This week in the JCI, new work from Jonathan Stamler’s lab at Case Western Reserve University shows that S-nitrosylation plays a key role in protecting against ischemic cardiac injury and heart failure. Mice expressing a mutation in humanized hemoglobin that prevented S-nitrosylation (C93A mice) experienced worse cardiac necrosis and function after induced myocardial infarction compared to mice expressing normal humanized hemoglobin. Loss of S-nitrosylation also led to adaptive cardiac vascularization and collateralization that was associated with partial mitigation of ischemic injury.
In the accompanying image, representative angiography shows the collateralized circulation of the left coronary artery through the left ventricle in a C93A mouse.
Homeostatic control of tissue oxygenation is achieved largely through changes in blood flow that are regulated by the classic physiological response of hypoxic vasodilation. The role of nitric oxide (NO) in the control of blood flow is a central tenet of cardiovascular biology. However, extensive evidence now indicates that hypoxic vasodilation entails
Rongli Zhang, Douglas T. Hess, James D. Reynolds, Jonathan S. Stamler