Stimulation of Erythrocyte Soluble Guanylyl Cyclase Induces cGMP Export and Cardioprotection in Type 2 Diabetes

• Published in: JACC. Basic to translational science 2023-08, Vol.8 (8), p.907-918
• Main Authors: Jiao, Tong, Collado, Aida, Mahdi, Ali, Tengbom, John, Tratsiakovich, Yahor, Milne, G. Todd, Alvarsson, Michael, Lundberg, Jon O., Zhou, Zhichao, Yang, Jiangning, Pernow, John
• Format: Article
• Language: English
• Subjects: Medicin och hälsovetenskap; Original Research - Clinical
• ISSN: 2452-302X; 2452-302X
• DOI: 10.1016/j.jacbts.2023.02.017

• RBCs from patients with T2D impair cardiac function after I/R. • Stimulation of sGC in RBCs induces release of a cardioprotective factor that protects from myocardial I/R injury. • sGC stimulation in RBCs causes release of cGMP and activation of cardiomyocyte PKG. • RBCs sGC provides a novel therapeutic target to prevent cardiac injury in T2D. Reduced nitric oxide (NO) bioactivity in red blood cells (RBCs) is critical for augmented myocardial ischemia-reperfusion injury in type 2 diabetes. This study identified the nature of “NO bioactivity” by stimulating the intracellular NO receptor soluble guanylyl cyclase (sGC) in RBCs. sGC stimulation in RBCs from patients with type 2 diabetes increased export of cyclic guanosine monophosphate from RBCs and activated cardiac protein kinase G, thereby attenuating ischemia-reperfusion injury. These results provide novel insight into RBC signaling by identifying cyclic guanosine monophosphate from RBC as a mediator of protection against cardiac ischemia-reperfusion injury induced by sGC stimulation in RBCs.