Key pointsr Skeletal muscle capillary regression is associated with elevated thrombospondin-1 and vascular endothelial growth factor protein expression with detraining.r Vascular endothelial growth factor and nucleolin responses to acute exercise are blunted in the triceps surae muscles following exercise training. In the plantaris and soleus muscles, this blunted response persists up to 28 days after cessation of training.r Effects of detraining on skeletal muscle microvascular density appears to be similar among skeletal muscle of varying oxidative potential and is poorly associated with expression of matrix metalloproteinases-2 and -9 and endostatin.Abstract Temporal expression of positive and negative angiogenic factors in response to detraining is poorly understood. We report the protein expression of anti-angiogenic peptides (thrombospondin-1, TSP-1; and endostatin) as well as pro-angiogenic factors (vascular endothelial growth factor, VEGF; matrix metalloproteinases-2 and -9), and nucleolin (a nuclear protein involved with synthesis and maturation of ribosomes) in response to detraining in triceps surae muscles of C57BL/6 mice. Male mice were allowed to exercise voluntarily for 21 days, and then basal and acute response to exercise were evaluated at 1, 7, 14 and 28 days detraining (D1, D7, D14, D28, respectively, n = 12/group). As seen in the D1 mice, training resulted in the increased muscle capillary-to-fibre ratio (C/F), increased maximal running time and elevated basal expression of VEGF and matrix metalloproteinase-9 (P < 0.05). After 7 days of detraining (D7), C/F levels were similar to control levels, but both basal VEGF and TSP-1 were elevated (P < 0.05). At D14 and D28, TSP-1 protein was not different compared to baseline levels; however, VEGF was elevated in gastrocnemius (GA), but not the soleus (SOL) or plantaris (PLT) muscles, of D14 mice. Endostatin tended to decrease in D14 and D28 compared to controls. Timing of nucleolin protein expression differed between muscle groups, with increases at D1, D7 and D14 in the PLT, SOL and GA muscles, respectively. The response of VEGF and nucleolin to acute exercise was blunted with training, and remained blunted in the PLT and SOL even after 28 days of detraining, at a time point long after muscle capillarization was observed to be similar to pre-training levels. These data suggest that TSP-1 may be a mediator of capillary regression with detraining, even in the face of elevated VEGF, suggesting that pro-angiogenic regulators may not be able to prevent the regression of skeletal muscle capillaries under physiological conditions. The responses of matrix metalloproteinases, endostatin and nucleolin poorly correlated with detraining-induced capillary regression.
Roadless areas are important for biodiversity maintenance and nature conservation but remain politically controversial due to conXicting interests of conservation and development. In this study, we applied a recently developed index of roadless volume (RV) across 67 counties of Alabama, USA as a case study to examine the relationships between roadless areas and local species richness. Our results indicated that with the increase of RV across counties, both the number of total Wsh and exotic Wsh species increased, but the relationship was not signiWcant for endemic Wsh species. The number of both herpetofaunal and plant species also increased with the increasing RV. For all included species, there was a signiWcant positive correlation between species richness and RV values. The number of endangered species decreased with the increase of RV per-capita. WildWre occurrences increased with the increase of RV. Preserving roadless areas is an important component of biodiversity conservation.
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