Alcicek Fatih Celal, Dybas Jakub, Bulat Katarzyna, Mohaissen Tasnim, Szczesny-Malysiak Ewa, Franczyk-Zarow Magdalena, Marzec Katarzyna M
Institute for Cardiovascular Physiology, Goethe University, Frankfurt, Germany.
Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Krakow, Poland.
Front Physiol. 2024 Nov 29;15:1497346. doi: 10.3389/fphys.2024.1497346. eCollection 2024.
Red blood cells (RBCs) play a role in the regulation of vascular tone via release of adenosine triphosphate (ATP) into the vasculature in response to various stimuli. Interestingly, ApoE/LDLR double-deficient (ApoE/LDLR) mice, a murine model of atherosclerosis, display a higher exercise capacity compared to the age-matched controls. However, it is not known whether increased exercise capacity in ApoE/LDLR mice is linked to the altered ATP release from RBCs. In this work, we characterized the ATP release feature of RBCs from ApoE/LDLR mice by exposing them to various stimuli . The results are linked to the previously reported mechanical and biochemical alterations in RBCs. 3V-induced ATP release from RBCs was at comparable levels for all groups, which indicated that the activity of adenylyl cyclase and the components of upstream signal-transduction pathway were intact. Moreover, hypoxia- and low pH-induced ATP release from RBCs was higher in ApoE/LDLR mice compared to their age-matched controls, a potential contributing factor and a finding in line with the higher exercise capacity. Taken together, augmented hypoxia-induced ATP release from RBCs in ApoE/LDLR mice indicates a possible deterioration in the ATP release pathway. This supports our previous reports on the role of the protein structure alterations of RBC cytosol in hypoxia-induced ATP release from RBCs in ApoE/LDLR mice. Thus, we emphasize that the presented herein results are the first step to future pharmacological modification of pathologically impaired microcirculation.
红细胞（RBCs）通过在各种刺激下向脉管系统释放三磷酸腺苷（ATP）来调节血管张力。有趣的是，载脂蛋白E/低密度脂蛋白受体双缺陷（ApoE/LDLR）小鼠，一种动脉粥样硬化的小鼠模型，与年龄匹配的对照组相比，具有更高的运动能力。然而，尚不清楚ApoE/LDLR小鼠运动能力的提高是否与红细胞ATP释放的改变有关。在这项研究中，我们通过将ApoE/LDLR小鼠暴露于各种刺激来表征其红细胞的ATP释放特征。这些结果与先前报道的红细胞机械和生化改变有关。所有组中3V诱导的红细胞ATP释放水平相当，这表明腺苷酸环化酶的活性和上游信号转导通路的成分是完整的。此外，与年龄匹配的对照组相比，ApoE/LDLR小鼠中缺氧和低pH诱导的红细胞ATP释放更高，这是一个潜在的促成因素，且这一发现与更高的运动能力一致。综上所述，ApoE/LDLR小鼠中红细胞缺氧诱导的ATP释放增加表明ATP释放途径可能恶化。这支持了我们之前关于ApoE/LDLR小鼠红细胞胞质溶胶蛋白质结构改变在缺氧诱导的红细胞ATP释放中的作用的报道。因此，我们强调本文所呈现的结果是未来对病理性受损微循环进行药理学修饰的第一步。
