Remodeling of skeletal muscle microvasculature in sickle cell trait and α-thalassemia

Abstract

The influence of sickle cell trait and/or α-thalassemia on skeletal muscle microvascular network characteristics was assessed and compared with control subjects [hemoglobin (Hb) AA] in 30 Cameroonian residents [10 HbAA, 5 HbAA α-thalassemia (α-t), 6 HbAS, and 9 HbASα-t] matched for maximal work capacity and daily energy expenditure. Subjects performed an incremental exercise to exhaustion and underwent a muscle biopsy. Muscle fiber type and surface area were not different among groups. However, sickle cell trait (SCT) was associated with lower capillary density ( P < 0.05), lower capillary tortuosity ( P < 0.001), and enlarged microvessels ( P < 0.01). SCT carriers had reduced counts of microvessels <5-μm diameter, but a higher percentage of broader microvessels, i.e., diameter >10 μm ( P < 0.05). α-Thalassemia seemed to be characterized by a higher capillary tortuosity and unchanged capillary density and diameter. Thus, while SCT is a priori clinically benign, we demonstrate for the first time that significant remodeling of the microvasculature occurs in SCT carriers. These modifications may possibly reflect protective adaptations against hemorheological and microcirculatory dysfunction induced by the presence of HbS. The remodeling of the microvascular network occurs to a lesser extent in α-thalassemia. In α-thalassemic subjects, increased capillary tortuosity would promote oxygen supply to muscle tissues and might compensate for the lower Hb content often reported in those subjects.

Effects of regular physical activity on skeletal muscle structural, energetic, and microvascular properties in carriers of sickle cell trait

“…However, the main changes observed in carriers of SCT consisted in their profound skeletal muscle microvasculature remodeling characterized by lower capillary density (CD) and tortuosity and a general enlargement of microvessels (55). Taken together, these latter results seem to indicate that carriers of SCT might be prone to impaired oxygen supply to and utilization by tissues that corroborates the results of Connes et al (13).…”

“…Second, the enlargement of the microvessels seems to compensate for the lower CD and tortuosity. Indeed, the product CD ϫ CSA that denotes microvascular blood supply, albeit very imperfectly (29), was not different in carriers of SCT compared with HbAA subjects (55). The results we report here in trained carriers of SCT show that the adaptations reported in less active carriers of SCT are amplified in the trained state.…”

“…Before giving their written consent, all subjects were fully informed of the objectives, possible discomforts, and potential benefits of the experiments. Part of the results has been published elsewhere for other purpose (55,56).…”

“…Indeed, an increasing number of studies (2,9,16,17,18,19,20,22,32,33,42,47,51,54,58) report nonfatal and fatal collapses, heat stroke, and rhabdomyolysis after exercise in subjects carrying SCT. Part of the severe exercise-related complications observed in carriers of SCT might be explained by hemorheological disorders, i.e., increased blood apparent viscosity and vascular adhesion, decreased RBC deformability, sickling, increased intravascular coagulation, and higher oxidative stress (4,13,14,40,43,44,48,55).…”

Microfluidic Study of Enhanced Deposition of Sickle Cells at Acute Corners

“…These features could play a major role in vaso-occlusion when coupled to the adhesive properties of SRBCs. Even though the structure and geometry of the microcirculatory network has been poorly documented in SCA patients, preliminary results in the skeletal muscle of patients with sickle cell trait (20), in the liver (21), or in the conjunctival microcirculation (22) of patients with Sickle Cell Disease indicate important changes: a rarefaction of microvessels in the network, a decrease of their tortuosity, and an enlargement of their diameter. These characteristics all point to a physiological relevance that remains to be understood in the context of RBC adhesion, stiffening, and flow.…”