Sex and genotype specificities of microvasculature and muscle remodeling in sub-Saharan sickle cell trait and disease

Abstract

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.