Altitude, Exercise, and Skeletal Muscle Angio-Adaptive Responses to Hypoxia: A Complex Story

Hypoxia, defined as a reduced oxygen availability, can be observed in many tissues in response to various physiological and pathological conditions. As a hallmark of the altitude environment, ambient hypoxia results from a drop in the oxygen pressure in the atmosphere with elevation. A hypoxic stress can also occur at the cellular level when the oxygen supply through the local microcirculation cannot match the cells’ metabolic needs. This has been suggested in contracting skeletal myofibers during physical exercise. Regardless of its origin, ambient or exercise-induced, muscle hypoxia triggers complex angio-adaptive responses in the skeletal muscle tissue. These can result in the expression of a plethora of angio-adaptive molecules, ultimately leading to the growth, stabilization, or regression of muscle capillaries. This remarkable plasticity of the capillary network is referred to as angio-adaptation. It can alter the capillary-to-myofiber interface, which represent an important determinant of skeletal muscle function. These angio-adaptive molecules can also be released in the circulation as myokines to act on distant tissues. This review addresses the respective and combined potency of ambient hypoxia and exercise to generate a cellular hypoxic stress in skeletal muscle. The major skeletal muscle angio-adaptive responses to hypoxia so far described in this context will be discussed, including existing controversies in the field. Finally, this review will highlight the molecular complexity of the skeletal muscle angio-adaptive response to hypoxia and identify current gaps of knowledges in this field of exercise and environmental physiology.

Malarial Related Myopathies: A Rhabdomyolysis Story

Malaria is amongst the most prevalent and epidemiologically relevant global parasitic protozoan infections. It is infecting millions of people annually, especially in south east Asia and sub Saharan Africa. Its morbidity and mortality still cannot be controlled entirely and elimination is still far away. Children and pregnant women are among the most vulnerable group in the population. Its pathobiology have related to cause direct or indirect deleterious effect on the patient’s skeletal muscle, named rhabdomyolysis. Eventhough it is very rare, but potentially fatal and lethal. Three mechanism of malaria related rhabdomyolysis are very intense inflammatory response, extensive red cells sequestration in muscle capillaries due to severe anemia and the parasite toxin’s, will lead to or add risks of complication. Derangement of specific type of muscle, named the skeletal and cardiac, is amongst the earliest sign of severe malaria. Further study need to be conducted in the future, especially on important topics about mechanism and its effect, signaling pathways, best practice on laboratory approach and management strategy best practice.

Trans-Endothelial Insulin Transport is Impaired in Skeletal Muscle Capillaries of Obese Male Mice

ABSTRACTDelivery of insulin to the surface of myocytes is required for skeletal muscle (SkM) insulin action. Previous studies have shown that SkM insulin delivery is reduced in the setting of obesity and insulin resistance (IR). The key variables that control SkM insulin delivery are 1) microvascular perfusion and 2) the rate at which insulin moves across the continuous endothelium of SkM capillaries. Obesity and IR are associated with reduced insulin-stimulated SkM perfusion. Whether an impairment in trans-endothelial insulin transport (EIT) contributes to SkM IR, however, is unknown. We hypothesized that EIT would be delayed in a mouse model of diet-induced obesity (DIO) and IR. Using intravital insulin imaging, we found that DIO male mice have a ~15% reduction in EIT compared to their lean counterparts. This impairment in EIT is associated with a 45% reduction in the density of endothelial vesicles. Despite impaired EIT, hyperinsulinemia sustained delivery of insulin to the interstitial space in DIO male mice. Even with maintained interstitial insulin delivery DIO male mice still showed SkM IR, indicating severe myocyellular IR in this model. Interestingly, there was no difference in EIT, endothelial ultrastructure or SkM insulin sensitivity between lean and high fat diet-fed female mice. These results suggest that, in male mice, obesity results in damage to the capillary endothelium which limits the capacity for EIT.