Attenuated cardiac post-ischemic injury and endothelial dysfunction by stimulation of soluble guanylyl cyclase in red blood cells from patients with type 2 diabetes

• Published in: EUROPEAN HEART JOURNAL 2021-10, Vol.42 (Supplement_1), p.3259
• Main Authors: Jiao, T, Zhou, Z, Mahdi, A, Tengbom, J, Tratsiakovich, Y, Yang, J, Pernow, J
• Format: Article
• Language: English
• Subjects: Medicin och hälsovetenskap
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehab724.3259

Abstract Background Reduced bioavailability of nitric oxide (NO) contributes to ischemic heart disease in type 2 diabetes (T2D). Red blood cells (RBCs) are known to produce NO bioactivity and to contain a functional soluble guanylyl cyclase (sGC) that is activated by NO. Recent studies revealed that RBCs from patients with T2D exacerbates ischemia-reperfusion (I/R) injury and induces endothelial dysfunction via a mechanism that is dependent on reduced export of NO bioactivity from RBCs. It remains unknown whether stimulation of sGC in RBCs from patients with T2D protects against myocardial I/R injury and endothelial dysfunction. Purpose To test the hypothesis that stimulation of sGC in RBCs from T2D patients protects against myocardial I/R injury and improves endothelial function. Methods RBCs collected from T2D patients and healthy subjects were incubated with vehicle or the sGC stimulator CYR715 before being administered to isolated Langendorff-perfused rat hearts subjected to 25 min global ischemia and 60 min reperfusion. Left ventricular developed pressure (LVDP) and infarct size were determined. In addition, isolated rat aortic rings were incubated with RBCs subsequent determination of endothelium-dependent relaxation (EDR). Results Administration of RBCs from T2D patients impaired post-ischemic recovery of LVDP and induced endothelial dysfunction in comparison with RBCs from healthy subjects (P