红细胞(RBC)的流变特性在其微循环中起着重要作用。RBC可以响应于机械力弹性变形以穿过狭窄的血管以在外周组织中进行有效的气体交换。在与生活方式相关的疾病如糖尿病中观察到红细胞变形性降低,高胆固醇血症,和高血压,这是与氧化应激增加和一氧化氮(NO)生物利用度降低有关的病理状况。红细胞细胞骨架蛋白上的氧化还原敏感半胱氨酸残基,如α-和β-血色素,负责膜的灵活性,受到长期氧化应激的影响,导致可逆和不可逆的氧化修饰和降低的红细胞变形性。然而,内源性,外源产生的NO通过用谷胱甘肽帽屏蔽氧化还原敏感的半胱氨酸残基来保护RBC膜的柔韧性免受进一步的氧化修饰。最近的研究表明,富含硝酸盐的饮食和适度的运动可以通过增加红细胞和血管内皮介导的微循环NO生物利用度之间的相互作用来增强NO的产生,从而增加RBC的可变形性。本文综述了RBC-和非RBC-介导NO产生的分子机制,以及饮食和运动来源的NO如何在与血管内皮功能障碍有关的生活方式相关疾病中预防红细胞变形能力降低。
The rheological properties of red blood cells (RBCs) play an important role in their microcirculation. RBCs can elastically deform in response to mechanical forces to pass through narrow vessels for effective gas exchange in peripheral tissues. Decreased RBC deformability is observed in lifestyle-related diseases such as diabetes mellitus, hypercholesterolemia, and hypertension, which are pathological conditions linked to increased oxidative stress and decreased nitric oxide (NO) bioavailability.
Redox-sensitive cysteine residues on RBC cytoskeletal proteins, such as α- and β-spectrins, responsible for membrane flexibility, are affected by prolonged oxidative stress, leading to reversible and irreversible oxidative modifications and decreased RBC deformability. However, endogenously, and exogenously generated NO protects RBC membrane flexibility from further oxidative modification by shielding
redox-sensitive cysteine residues with a glutathione cap. Recent studies have shown that nitrate-rich diets and moderate exercise can enhance NO production to increase RBC deformability by increasing the interplay between RBCs and vascular endothelium-mediated NO bioavailability for microcirculation. This
review focuses on the molecular mechanism of RBC- and non-RBC-mediated NO generation, and how diet- and exercise-derived NO exert prophylactic effects against decreased RBC deformability in lifestyle-related diseases with vascular endothelial dysfunction.