Evidence for a Profound Remodeling of Skeletal Muscle and Its Microvasculature in Sickle Cell Anemia

Abstract

Sickle cell anemia (SCA) is a hemoglobinopathy leading to major hematologic, hemorheologic, and hemodynamic disorders that induce various complications, including organ failure, and ultimately lead to death. Here, we assessed for the first time repercussions of SCA on skeletal muscle and its microvasculature. Twenty-seven sedentary Cameroonian volunteer men participated in the study. They were assigned to one of three groups according to their hemoglobin status (healthy control subjects, n = 10; sickle cell trait carriers, n = 10; and SCA patients, n = 7) and underwent muscle biopsy of the vastus lateralis. SCA was associated with microvessel rarefaction, decrease in capillary tortuosity, and widening of microvessel diameter. The absence of capillary wall reinforcement was shown by lack of wall thickening and lack of fibrous tissue or smooth muscle in their constitution. We also observed changes in fiber type distribution, muscle atrophy, an increase in satellite cell number, and a decrease in activity of creatine kinase and several oxidative enzymes. No signs of tissue necrosis, inflammatory stress, fibrosis, or segmented fibers were observed. The present study highlighted marked effects of SCA on microvascular, structural, and energetic characteristics of skeletal muscle.