Blervaque Léo, Bartolucci Pablo, Riccetti Manon, Ravelojaona Marion, Merlet Angèle N, Noguer Mathilde, Rojo Manon, Hourdé Christophe, Martin Cyril, Pialoux Vincent, Gellen Barnabas, Galactéros Frédéric, Oyono-Enguéllé Samuel, Féasson Léonard, Messonnier Laurent A
Laboratoire Interuniversitaire de Biologie de la Motricité, Université Savoie Mont Blanc, Chambéry, France.
Unité de Recherche Clinique, Centre Hospitalier Métropole Savoie, Chambéry, France.
Blood Adv. 2025 Sep 23;9(18):4661-4672. doi: 10.1182/bloodadvances.2024015657.
Sickle cell disease (SCD) is associated with microvascular and muscle remodeling as well as reduced exercise tolerance. However, SCD repercussions on microvasculature and muscle in women remain unknown. This study aimed to compare (1) muscle microvascular and energetic characteristics of female and male healthy individuals (CON), carriers of sickle cell trait (SCT), and patients with SCD; and (2) adaptations to endurance training (ET) compared with habitual life (untrained [UT]) in patients. In SCD, correlations between capillary density and plasma L-selectin and intercellular adhesion molecule and between capillary diameter and mean corpuscular hemoglobin S concentration were noticed (P < .01 all). The capillary network rarefaction observed in SCD was more pronounced in women than in men (interaction: P < .01). Muscle hypoxia markers were not different between groups. Compared with CON, the surface area for 100 myocytes was lower in men with SCD (both P < .001) but not in women. Advanced oxidation protein products were increased in patients with SCD and to a greater extent in men (interaction: P < .02). Components of muscle pH regulation were specifically higher in SCT. Compared with UT, ET saw its microvascular network and oxidative capacities increase, without differences between men and women. Our results suggest that SCD-associated capillary rarefaction and enlargement could be related to disturbed hemodynamics and reduced erythrocytes deformability, respectively. The specific remodeling in female patients with SCD included aggravated microvascular remodeling but preserved myocytes. Muscle pH regulation mechanisms appeared specifically upregulated in carriers of SCT. Men and women with SCD improved similarly their microvasculature and muscle energetic characteristics in response to ET.
镰状细胞病（SCD）与微血管和肌肉重塑以及运动耐力降低有关。然而，SCD对女性微血管和肌肉的影响仍不清楚。本研究旨在比较：（1）健康女性和男性个体（CON）、镰状细胞性状携带者（SCT）和SCD患者的肌肉微血管和能量特征；（2）患者耐力训练（ET）与习惯生活（未训练[UT]）相比的适应性变化。在SCD患者中，发现毛细血管密度与血浆L-选择素和细胞间黏附分子之间以及毛细血管直径与平均血红蛋白S浓度之间存在相关性（均P < 0.01）。SCD患者中观察到的毛细血管网络稀疏在女性中比男性更明显（交互作用：P < 0.01）。各组之间的肌肉缺氧标志物无差异。与CON组相比，SCD男性患者100个心肌细胞的表面积较低（均P < 0.001），但女性患者无此现象。SCD患者的晚期氧化蛋白产物增加，男性增加程度更大（交互作用：P < 0.02）。肌肉pH调节成分在SCT患者中特别高。与UT组相比，ET组的微血管网络和氧化能力增加，男女之间无差异。我们的结果表明，SCD相关的毛细血管稀疏和扩张可能分别与血流动力学紊乱和红细胞变形性降低有关。女性SCD患者的特异性重塑包括微血管重塑加重但心肌细胞保留。肌肉pH调节机制在SCT携带者中似乎特别上调。SCD男性和女性患者对ET的反应相似，其微血管和肌肉能量特征均得到改善。
