Capillary Supply Research Articles

Evaluation of the 18-bp deletion/insertion variant of the VEGF gene in athletes

The skeletal muscle capillary supply mainly determines the highest exercise capacity. Vascular endothelial growth factor (VEGF) is the major growth factor during the angiogenesis process. Therefore, we aimed to investigate whether the VEGF insertion/deletion (I/D) variant differs between athletes and sedentary controls in the Turkish population. Three hundred sixteen subjects, including 146 athletes from different branches and 170 sedentary people, voluntarily participated in this study. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) analysis for the VEGF I/D variant. The results were evaluated statistically. In this study, the athletes and the controls showed a statistically significant difference in the genotype and allele distribution of the VEGF I/D variant. The athletes had a more prevalent D allele and D/D genotype than the controls (p = 0.008 and p = 0.034, respectively). There was a statistically significant association between the patients and the controls in terms of D/D vs. I/I + I/D genotypes (p = 0.018). There was no significant difference in VEGF I/D genotype distribution according to sports branches. Athletic performance is a complex trait influenced by genetic and environmental factors. As far as we know, this is the first study to evaluate the VEGF I/D variant in athletes in Turkey. According to our results in this study, we concluded that the VEGF I/D variant, D/D genotype, and D allele are associated with sport performance in the Turkish population. However, there is a need for studies with large samples in which environmental and emotional factors will also be taken into account.

Skeletal muscle adaptation to indirect electrical stimulation: divergence between microvascular and metabolic adaptations.

What is the central question of this study? Can we manipulate muscle recruitment to differentially enhance skeletal muscle fatigue resistance? What is the main finding and its importance? Through manipulation of muscle activation patterns, it is possible to promote distinct microvascular growth. Enhancement of fatigue resistance is closely associated with the distribution of the capillaries within the muscle, not necessarily with quantity. Additionally, at the acute stages of remodelling in response to indirect electrical stimulation, the improvement in fatigue resistance appears to be primarily driven by vascular remodelling, with metabolic adaptation of secondary importance. Exercise involves a complex interaction of factors influencing muscle performance, where variations in recruitment pattern (e.g., endurance vs. resistance training) may differentially modulate the local tissue environment (i.e., oxygenation, blood flow, fuel utilization). These exercise stimuli are potent drivers of vascular and metabolic change. However, their relative contribution to adaptive remodelling of skeletal muscle and subsequent performance is unclear. Using implantable devices, indirect electrical stimulation (ES) of locomotor muscles of rat at different pacing frequencies (4, 10 and 40Hz) was used to differentially recruit hindlimb blood flow and modulate fuel utilization. After 7days, ES promoted significant remodelling of microvascular composition, increasing capillary density in the cortex of the tibialis anterior by 73%, 110% and 55% for the 4Hz, 10 and 40Hz groups, respectively. Additionally, there was remodelling of the whole muscle metabolome, including significantly elevated amino acid turnover, with muscle kynurenic acid levels doubled by pacing at 10Hz (P<0.05). Interestingly, the fatigue index of skeletal muscle was only significantly elevated in 10Hz (58% increase) and 40Hz (73% increase) ES groups, apparently linked to improved capillary distribution. These data demonstrate that manipulation of muscle recruitment pattern may be used to differentially expand the capillary network prior to altering the metabolome, emphasising the importance of local capillary supply in promoting exercise tolerance.

Capillary rarefaction during bed rest is proportionally less than fibre atrophy and loss of oxidative capacity.

Muscle disuse from bed rest or spaceflight results in losses in muscle mass, strength and oxidative capacity. Capillary rarefaction may contribute to muscle atrophy and the reduction in oxidative capacity during bed rest. Artificial gravity may attenuate the negative effects of long-term space missions or bed rest. The aim of the present study was to assess (1) the effects of bed rest on muscle fibre size, fibre type composition, capillarization and oxidative capacity in the vastus lateralis and soleus muscles after 6 and 55days of bed rest and (2) the effectiveness of artificial gravity in mitigating bed-rest-induced detriments to these parameters. Nineteen participants were assigned to a control group (control, n=6) or an intervention group undergoing 30min of centrifugation (n=13). All underwent 55days of head-down tilt bed rest. Vastus lateralis and soleus biopsies were taken at baseline and after 6 and 55days of bed rest. Fibre type composition, fibre cross-sectional area, capillarization indices and oxidative capacity were determined. After just 6days of bed rest, fibre atrophy (-23.2±12.4%, P<0.001) and reductions in capillary-to-fibre ratio (C:F; 1.97±0.57 vs. 1.56±0.41, P<0.001) were proportional in both muscles as reflected by a maintained capillary density. Fibre atrophy proceeded at a much slower rate between 6 and 55days of bed rest (-11.6±12.1% of 6days, P=0.032) and was accompanied by a 19.1% reduction in succinate dehydrogenase stain optical density (P<0.001), without any further significant decrements in C:F (1.56±0.41 vs. 1.49±0.37, P=0.459). Consequently, after 55days of bed rest, the capillary supply-oxidative capacity ratio of a fibre had increased by 41.9% (P<0.001), indicating a capillarization in relative excess of oxidative capacity. Even though the heterogeneity of capillary spacing (LogR SD) was increased after 55days by 12.7% (P=0.004), tissue oxygenation at maximal oxygen consumption of the fibres was improved after 55days bed rest. Daily centrifugation failed to blunt the bed-rest-induced reductions in fibre size and oxidative capacity and capillary rarefaction. The relationship between fibre size and oxidative capacity with the capillary supply of a fibre is uncoupled during prolonged bed rest as reflected by a rapid loss of muscle mass and capillaries, followed at later stages by a more than proportional loss of mitochondria without further capillary loss. The resulting excessive capillary supply of the muscle after prolonged bed rest is advantageous for the delivery of substrates needed for subsequent muscle recovery.

Resting Rates of Blood Flow and Glucose Use per Neuron Are Proportional to Number of Endothelial Cells Available per Neuron Across Sites in the Rat Brain.

We report in a companion paper that in the mouse brain, in contrast to the 1,000-fold variation in local neuronal densities across sites, capillary density (measured both as capillary volume fraction and as density of endothelial cells) show very little variation, of the order of only fourfold. Here we confirm that finding in the rat brain and, using published rates of local blood flow and glucose use at rest, proceed to show that what small variation exists in capillary density across sites in the rat brain is strongly and linearly correlated to variations in local rates of brain metabolism at rest. Crucially, we show that such variations in local capillary density and brain metabolism are not correlated with local variations in neuronal density, which contradicts expectations that use-dependent self-organization would cause brain sites with more neurons to have higher capillary densities due to higher energetic demands. In fact, we show that the ratio of endothelial cells per neuron serves as a linear indicator of average blood flow and glucose use per neuron at rest, and both increase as neuronal density decreases across sites. In other words, because of the relatively tiny variation in capillary densities compared to the large variation in neuronal densities, the anatomical infrastructure of the brain is such that those sites with fewer neurons have more energy supplied per neuron, which matches a higher average rate of energy use per neuron, compared to sites with more neurons. Taken together, our data support the interpretation that resting brain metabolism is not demand-based, but rather limited by its capillary supply, and raise multiple implications for the differential vulnerability of diverse brain areas to disease and aging.

Implication of satellite cell behaviors in capillary growth via VEGF expression-independent mechanism in response to mechanical loading in HeyL-null mice.

Angiogenesis and muscle satellite cell (SC)-mediated myonuclear accretion are considered essential for the robust response of contraction-induced muscle hypertrophy. Moreover, both myonucleus and SCs are physically adjacent to capillaries and are the major sites for the expression of proangiogenic factors, such as VEGF, in the skeletal muscle. Thus, events involving the addition of new myonuclei via activation of SCs may play an important role in angiogenesis during muscle hypertrophy. However, the relevance among myonuclei number, capillary supply, and angiogenesis factor is not demonstrated. The Notch effector HeyL is specifically expressed in SCs in the skeletal muscle and is crucial for SC proliferation by inhibiting MyoD in overload-induced muscle hypertrophy. Here, we tested whether the addition of new myonuclei by SC in overloaded muscle is associated with angiogenic adaptation by reanalyzing skeletal muscle from HeyL-knockout (KO) mice, which show blunted responses of SC proliferation, myonucleus addition, and overload-induced muscle hypertrophy. Reanalysis confirmed blunted SC proliferation and myonuclear accretion in the plantaris muscle of HeyL-KO mice 9 wk after synergist ablation. Interestingly, the increase in capillary-to-fiber ratio observed in wild-type (WT) mice was impaired in HeyL-KO mice. In both WT and HeyL-KO mice, the expression of VEGFA and VEGFB was similarly increased in response to overload. In addition, the expression pattern of TSP-1, a negative regulator of angiogenesis, was also not changed between WT and HeyL-KO mice. Collectively, these results suggest that SCs activation-myonuclear accretion plays a crucial role in angiogenesis during overload-induced muscle hypertrophy via independent of angiogenesis regulators.

Effect of Micro Honeycomb Porous Plate on the Critical Heat Flux in Saturated Pool Boiling

Enhancement of the critical heat flux in pool boiling by the attachment of a micro HPP on a heated surface is investigated experimentally using water under saturated boiling conditions. HPP enhance the CHF from the capillary supply of liquid onto the heated surface through the pores and the release of vapor generated through the channels. When the height of the micro HPP on the heated surface is 1.4 mm, the CHF increases to 2.5 MW/m2. While the CHF began to decrease when the thickness was more than1.4 mm. In regions of thin HPP thickness, the CHF can be explained by the Haramura-Katto model. Therefore, in this presentation we examined the CHF mechanism in the thicker HPP region using the capillary limit model.

Myofibre injury induces capillary disruption and regeneration of disorganized microvascular networks.

Injury to skeletal muscle disrupts myofibres and their microvascular supply. While the regeneration of myofibres is well described, little is known of how the microcirculation is affected by skeletal muscle injury or its recovery during regeneration. Nevertheless, the microvasculature must also recover to restore skeletal muscle function. We aimed to define the nature of microvascular damage and time course of repair during muscle injury and regeneration induced by the myotoxin BaCl2 . To test the hypothesis that microvascular disruption occurred secondary to myofibre injury, isolated microvessels were exposed to BaCl2 or the myotoxin was injected into the gluteus maximus (GM) muscle of mice. In isolated microvessels, BaCl2 depolarized smooth muscle cells (SMCs) and endothelial cells while increasing intracellular calcium in SMCs but did not elicit death of either cell type. At 1day post-injury (dpi) of the GM, capillary fragmentation coincided with myofibre degeneration while arteriolar and venular networks remained intact; neutrophil depletion before injury did not prevent capillary damage. Perfused capillary networks reformed by 5dpi in association with more terminal arterioles and were dilated through 10dpi. With no change in microvascular area or branch point number in regenerating capillary networks, fewer capillaries aligned with myofibres and were no longer organized into microvascular units. By 21dpi, capillary orientation and microvascular unit organization were no longer different from uninjured GM. We conclude that following their disruption secondary to myofibre damage, capillaries regenerate as disorganized networks that remodel into microvascular units as regenerated myofibres mature. KEY POINTS: Skeletal muscle regenerates after injury; however, the nature of microvascular damage and repair is poorly understood. Here, the myotoxin BaCl2 , a standard experimental method of acute skeletal muscle injury, was used to investigate the response of the microcirculation to local injury of intact muscle. Intramuscular injection of BaCl2 induced capillary fragmentation with myofibre degeneration; arteriolar and venular networks remained intact. Direct exposure to BaCl2 did not kill microvascular endothelial cells or smooth muscle cells. Dilated capillary networks reformed by 5days post-injury (dpi) in association with more terminal arterioles. Capillary orientation remained disorganized through 10dpi. Capillaries realigned with myofibres and reorganized into microvascular units by 21dpi, which coincides with the recovery of vasomotor control and maturation of nascent myofibres. Skeletal muscle injury disrupts its capillary supply secondary to myofibre degeneration. Reorganization of regenerating microvascular networks accompanies the recovery of blood flow regulation.

Heterogeneity in form and function of the rat extensor digitorum longus motor unit.

The motor unit comprises a variable number of muscle fibres that connect through myelinated nerve fibres to a motoneuron (MN), the central drivers of activity. At the simplest level of organisation there exist phenotypically distinct MNs that activate corresponding muscle fibre types, but within an individual motor pool there typically exists a mixed population of fast and slow firing MNs, innervating groups of Type II and Type I fibres, respectively. Characterising the heterogeneity across multiple levels of motor unit organisation is critical to understanding changes that occur in response to physiological and pathological perturbations. Through a comprehensive assessment of muscle histology and ex vivo function, mathematical modelling and neuronal tracing, we demonstrate regional heterogeneities at the level of the MN, muscle fibre type composition and oxygen delivery kinetics of the rat extensor digitorum longus (EDL) muscle. Specifically, the EDL contains two phenotypically distinct regions: a relatively oxidative medial and a more glycolytic lateral compartment. Smaller muscle fibres in the medial compartment, in combination with a greater local capillary density, preserve tissue O2 partial pressure (PO2) during modelled activity. Conversely, capillary supply to the lateral compartment is calculated to be insufficient to defend active muscle PO2 but is likely optimised to facilitate metabolite removal. Simulation of in vivo muscle length change and phasic activation suggest that both compartments are able to generate similar net power. However, retrograde tracing demonstrates (counter to previous observations) that a negative relationship between soma size and C‐bouton density exists. Finally, we confirm a lack of specificity of SK3 expression to slow MNs. Together, these data provide a reference for heterogeneities across the rat EDL motor unit and re‐emphasise the importance of sampling technique.

Comparison of Shifts in Skeletal Muscle Plasticity Parameters in Horses in Three Different Muscles, in Answer to 8 Weeks of Harness Training.

Training-induced follow-up of multiple muscle plasticity parameters in postural stability vs. locomotion muscles provides an integrative physiological view on shifts in the muscular metabolic machinery. It can be expected that not all muscle plasticity parameters show the same expression time profile across muscles. This knowledge is important to underpin results of metabolomic studies. Twelve non-competing Standardbred mares were subjected to standardized harness training. Muscle biopsies were taken on a non-training day before and after 8 weeks. Shifts in muscle fiber type composition and muscle fiber cross-sectional area (CSA) were compared in the m. pectoralis, the m. vastus lateralis, and the m. semitendinosus. In the m. vastus lateralis, which showed most pronounced training-induced plasticity, two additional muscle plasticity parameters (capillarization and mitochondrial density) were assessed. In the m. semitendinosus, additionally the mean minimum Feret's diameter was assessed. There was a significant difference in baseline profiles. The m. semitendinosus contained less type I and more type IIX fibers compatible with the most pronounced anaerobic profile. Though no baseline fiber type-specific and overall mean CSA differences could be detected, there was a clear post-training decrease in fiber type specific CSA, most pronounced for the m. vastus lateralis, and this was accompanied by a clear increase in capillary supply. No shifts in mitochondrial density were detected. The m. semitendinosus showed a decrease in fiber type specific CSA of type IIAX fibers and a decrease of type I fiber Feret's diameter as well as mean minimum Feret's diameter. The training-induced increased capillary supply in conjunction with a significant decrease in muscle fiber CSA suggests that the muscular machinery models itself toward an optimal smaller individual muscle fiber structure to receive and process fuels that can be swiftly delivered by the circulatory system. These results are interesting in view of the recently identified important fuel candidates such as branched-chain amino acids, aromatic amino acids, and gut microbiome-related xenobiotics, which need a rapid gut–muscle gateway to reach these fibers and are less challenging for the mitochondrial system. More research is needed with that respect. Results also show important differences between muscle groups with respect to baseline and training-specific modulation.

Influence of Age and Breed on Bovine Ovarian Capillary Blood Supply, Ovarian Mitochondria and Telomere Length

Worldwide, dairy cows of the type of high-producing cattle (HPC) suffer from health and fertility problems at a young age and therefore lose productivity after an average of only three lactations. It is still contentious whether these problems are primarily due to genetics, management, feeding or other factors. Vascularization plays a fundamental role in the cyclic processes of reproductive organs, as well as in the regeneration of tissues. In a previous study, HPC were shown to have a greater ovarian corpus luteum vascularization compared to dual-purpose breeds. We hypothesize that this activated angiogenesis could likely lead to an early exhaustion of HPC′s regenerative capacity and thus to premature reproductive senescence. The objective of this study was to investigate if a HPC breed (Holstein-Friesian, HF) exhibits higher ovarian angiogenesis than a dual-purpose breed (Polish Red cow, PR) and if this is related to early ovarian aging and finally reproductive failure. For this purpose, we assessed the degree of vascularization by means of ovarian blood vessel characterization using light microscopy. As indicators for aging, we measured ovarian mitochondrial size and telomere length in peripheral leukocytes. We report in this study that in both breeds the distance between capillaries became smaller with increasing age and that the mean telomere length decreased with increasing age. The only difference between the two breeds was that PR developed larger capillaries than HF. Neither a relationship between telomere length, nor the morphology of the mitochondrial apparatus and nor angiogenesis in HF was proven. Although the data trends indicated that the proportion of shortened telomeres in HF was higher than in the PR, no significant difference between the two breeds was detected.

Myocardial angiogenesis induced by exercise training involves a regulatory mechanism mediated by kinin receptors

ABSTRACT Objective: To demonstrate that the kallikrein-kinin system (KKS) is upstream of angiogenic signaling pathway, and to determine the role of the kinin B1 and B2 receptors in myocardial angiogenesis induced by exercise training. Methods: Forty Wistar rats were randomly assigned to an exercise control (EC) group, a B1 receptor antagonist (B1Ant) group, a B2 receptor antagonist (B2Ant) group, and a double receptor antagonist ((B1+ B2)Ant) group. A myocardial infarction model was employed. Animals in all groups received 30 min of exercise training for 4 weeks. The expression of VEGF and eNOS, capillary supply, and apoptosis rate were evaluated. Results: The mRNA and protein expression of VEGF and eNOS showed similar trends in all groups, and were lowest in the (B1+ B2) Ant group, and highest in the EC group. Levels of VEGF and eNOS mRNA were significantly lower in the B1Ant group than in the B2Ant group (p< .001 and p< .05, respectively). VEGF and eNOS protein in the B1Ant group was also significantly lower (p< .01 and p< .05, respectively) than in the B2Ant group. The capillary numbers in the (B1+ B2) Ant group were significantly lower than in the EC group (395.8 ± 105 vs. 1127.9 ± 192.98, respectively). The apoptosis rate of cardiomyocytes was highest in the (B1+ B2) Ant group. Conclusion: KKS may act as an upstream signal transduction pathway for angiogenic factors in myocardial angiogenesis. The B1 and B2 receptors exert additive effects, and the B1 receptor has the most prominent role in mediating KKS-induced myocardial angiogenesis.

Blood-flow-restricted exercise: Strategies for enhancing muscle adaptation and performance in the endurance-trained athlete.

What is the topic of this review? Blood-flow-restricted (BFR) exercise represents a potential approach to augment the adaptive response to training and improve performance in endurance-trained individuals. What advances does it highlight? When combined with low-load resistance exercise, low- and moderate-intensity endurance exercise and sprint interval exercise, BFR can provide an augmented acute stimulus for angiogenesis and mitochondrial biogenesis. These augmented acute responses can translate into enhanced capillary supply and mitochondrial function, and subsequent endurance-type performance, although this might depend on the nature of the exercise stimulus. There is a requirement to clarify whether BFR training interventions can be used by high-performance endurance athletes within their structured training programme. A key objective of the training programme for an endurance athlete is to optimize the underlying physiological determinants of performance. Training-induced adaptations are governed by physiological and metabolic stressors, which initiate transcriptional and translational signalling cascades to increase the abundance and/or function of proteins to improve physiological function. One important consideration is that training adaptations are reduced as training status increases, which is reflected at the molecular level as a blunting of the acute signalling response to exercise. This review examines blood-flow-restricted (BFR) exercise as a strategy for augmenting exercise-induced stressors and subsequent molecular signalling responses to enhance the physiological characteristics of the endurance athlete. Focus is placed on the processes of capillary growth and mitochondrial biogenesis. Recent evidence supports that BFR exercise presents an intensified training stimulus beyond that of performing the same exercise alone. We suggest that this has the potential to induce enhanced physiological adaptations, including increases in capillary supply and mitochondrial function, which can contribute to an improvement in performance of endurance exercise. There is, however, a lack of consensus regarding the potency of BFR training, which is invariably attributable to the different modes, intensities and durations of exercise and BFR methods. Further studies are needed to confirm its potential in the endurance-trained athlete.

Remote Sensing Monitoring Method for Groundwater Level on Aeolian Desertification Area

Groundwater is one of the most important natural resources. Regional groundwater depth is an important parameter for understanding groundwater resources and maintaining sustainable development of water resources and environment. The middle reaches of the Tarim River in Xinjiang are the most primitive and well-preserved place in the world, which provides valuable resources in studying the response mechanism of surface vegetation to the groundwater level. The ecological environment of Tarim River Basin has been deteriorating, and Populuseuphratica forest has died, which is directly related to the decrease of water inflow and groundwater level around the Tarim River. To obtain the spatial distribution of the groundwater level, this study uses the MODIS satellite remote sensing image data and the remote sensing-mathematical-model of a fusion science research methods, based on the field investigation of the groundwater level, soil moisture, and other supporting information on Aeolian desertification area in the middle reaches of Tarim River in Xinjiang. Through the experimental equation of the soil moisture and groundwater level, a simple and effective remote sensing method was proposed. This method is used to evaluate the spatial distribution of groundwater level based on the MODIS image data when there is capillary supply in the soil. This model was field-proven on the desertification area in the middle reaches of Tarim River. The results indicate that the correlation coefficient between the inversion of groundwater depth and the measured groundwater level is 0.89, which are realistic with small errors. So it is feasible to monitor and assess the spatial distribution of groundwater table depth in desertification areas with a large groundwater depth of 6 m or less. This study is helpful to provide critical area for the ecological environment monitoring and restoration, and ultimately serve the sustainable development of water and environment.

Skeletal muscle of females and males with constitutional thinness: a low intramuscular lipid content and oxidative profile.

Constitutional thinness (CT) is a nonpathological state of underweight. The current study aimed to explore skeletal muscle energy storage in individuals with CT and to further characterize muscle phenotype at baseline and in response to overfeeding. Thirty subjects with CT (15 females, 15 males) and 31 normal-weight control subjects (16 females, 15 males) participated in the study. Histological and enzymological analyses were performed on muscle biopsy specimens before and after overfeeding. In the skeletal muscle of CT participants compared with controls, we observed a lower content of intramuscular triglycerides for type I (-17%, p < 0.01) and type IIA (-14%, p < 0.05) muscle fibers, a lower glycogen content for type I (-6%, p < 0.01) and type IIA (-5%, p < 0.05) muscle fibers, a specific fiber-type distribution, a marked muscle hypotrophy (-20%, p < 0.001), a low capillary-to-fiber ratio (-19%, p < 0.001), and low citrate synthase activity (-18%, p < 0.05). In response to overfeeding, CT participants increased their intramuscular triglycerides content in type I (+10%, p < 0.01) and type IIA (+9%, p < 0.01) muscle fibers. CT individuals seem to present an unusual muscle phenotype and different adaptations to overfeeding compared with normal-weight individuals, suggesting a specific energy metabolism and muscle adaptations. ClinicalTrials.gov registration no. NCT02004821. Novelty Low intramuscular triglycerides and glycogen content in skeletal muscle of constitutionally thin individuals. Low oxidative capacity, low capillary supply, and fiber hypotrophy in skeletal muscle of constitutionally thin individuals. Increase in intramuscular triglycerides in constitutional thinness in response to overfeeding.

Synergistic effect of vascular endothelial growth factor gene inactivation in endothelial cells and skeletal myofibres on muscle enzyme activity, capillary supply and endurance exercise in mice.

What is the central question of this study? Does vascular endothelial growth factor (VEGF) expressed by both endothelial cells and skeletal myofibres maintain the number of skeletal muscle capillaries and regulate endurance exercise? What is the main finding and its importance? VEGF expressed by both endothelial cells and skeletal myofibres is not essential for maintaining capillary number but does contribute to exercise performance. Many chronic diseases lead to exercise intolerance, with loss of skeletal muscle capillaries. While many muscle cell types (myofibres, satellite cells, endothelial cells, macrophages and fibroblasts) express vascular endothelial growth factor (VEGF), most muscle VEGF is stored in myofibre vesicles which can release VEGF to signal VEGF receptor-expressing cells. VEGF gene ablation in myofibres or endothelial cells alone does not cause capillary regression. We hypothesized that simultaneously deleting the endothelial cell (EC) and skeletal myofibre (Skm) VEGF gene would cause capillary regression and impair exercise performance. This was tested in adult mice by simultaneous conditional deletion of the VEGF gene (Skm/EC-VEGF-/- mice) through the use of VEGFLoxP, HSA-Cre-ERT2 and PDGFb-iCre-ERT2 transgenes. These double-deletion mice were compared to three control groups - WT, EC VEGF gene deletion alone and myofibre VEGF gene deletion alone. Three weeks after initiating gene deletion, Skm/EC-VEGF-/- mice, but not SkmVEGF-/- or EC-VEGF-/- mice, reached exhaustion 40min sooner than WT mice in treadmill tests (P=0.002). WT, SkmVEGF-/- and EC-VEGF-/- , but not Skm/EC-VEGF-/- , mice gained weight over the 3weeks. Capillary density, fibre area and capillary: fibre ratio in soleus, plantaris, gastrocnemius and cardiac papillary muscle were similar across the groups. Phosphofructokinase and pyruvate dehydrogenase activities increased only in Skm/EC-VEGF-/- mice. These data suggest that deletion of the VEGF gene simultaneously in endothelial cells and myofibres, while reducing treadmill endurance and despite compensatory augmentation of glycolysis, is not required for muscle capillary maintenance. Reduced endurance remains unexplained, but may possibly be related to a role for VEGF in controlling perfusion of contracting muscle.

Sex Differences In Quadriceps Angiogenic Signaling And Muscle Capillary Supply After ACL Injury

Following an Anterior Cruciate Ligament (ACL) reconstruction, females have worse functional outcomes; however, skeletal muscle biology has preferentially been studied in males. Muscle adaptation and recovery from injury are intimately tied to the muscle capillary network, which delivers oxygen, nutrients, and hormones to muscle fibers. PURPOSE: To examine differences in skeletal muscle angiogenic signaling and capillary supply in males and females after ACL injury. METHODS: Vastus lateralis (VL) biopsies were collected (24.6 ± 5.5 yr; 8M, 5F) from the ACL injured (INJ) and non-injured (NI) leg before reconstruction. Samples were assessed for vascular endothelial growth factor receptor 1 and 2 (VEGFR1 and VEGFR2) by western blot. Capillary to fiber ratio (C:F), capillary to fiber perimeter exchange index (CFPE), and capillary tortuosity (% fiber border directly contacting capillary wall) were assessed by immunohistochemistry. RESULTS: The percentage of phosphorylated relative to total VEGFR2 was not different between INJ and NI, but was lower in females (76.9 ± 4.1%) compared to males (89.2 ± 3.2%; P = 0.043). VEGFR2 abundance tended to be higher (P = 0.098) and C:F was lower (INJ: 2.3 ± 0.2 capillary•fiber-1, NI: 2.6 ± 0.2 capillary•fiber-1; P = 0.018) in INJ compared to NI, but neither parameter was different between sexes. VEGFR1 abundance displayed a sex by injury interaction (P = 0.004), with females having greater abundance of VEGFR1 in INJ (548 ± 54 A.U.) compared to NI (478 ± 53 A.U.; P = 0.050), while males showed the opposite (NI: 461 ± 42 A.U., INJ: 383 ± 42 A.U.). CFPE was lower in INJ compared to NI (INJ: 5.1 ± 0.3 capillary•1000μm-1, NI: 5.8 ± 0.3 capillary•1000μm-1; P = 0.002), and post-hoc analysis revealed that the difference was driven by females. Capillary tortuosity was lower in INJ (13 ± 2%) compared to NI (17 ± 2%) for females only (P = 0.006). CONCLUSION: Differences in angiogenic signaling between males and females in both INJ and NI limbs were evident, and ACL injury resulted in an exacerbated deficit in muscle capillary supply for females. These results support the idea that sex-specific differences in VL capillary network remodeling following ACL injury contribute to different functional outcomes following reconstruction and rehabilitation. Supported by NIH grants: R01 AR072061 and K23 AR062069.

Resistance exercise training promotes fiber type-specific myonuclear adaptations in older adults.

Aging induces physiological decline in human skeletal muscle function and morphology, including type II fiber atrophy and an increase in type I fiber frequency. Resistance exercise training (RET) is an effective strategy to overcome muscle mass loss and improve strength, with a stronger effect on type II fibers. In the present study, we sought to determine the effect of a 12-wk progressive RET program on the fiber type-specific skeletal muscle hypertrophic response in older adults. Nineteen subjects [10 men and 9 women (71.1 ± 4.3 yr)] were studied before and after the 12-wk program. Immunohistochemical analysis was used to quantify myosin heavy chain (MyHC) isoform expression, cross-sectional area (CSA), satellite cell abundance, myonuclear content, and lipid droplet density. RET induced an increase in MyHC type II fiber frequency and a concomitant decrease in MyHC type I fiber frequency. Mean CSA increased significantly only in MyHC type II fibers (+23.3%, P < 0.05), but myonuclear content increased only in MyHC type I fibers (P < 0.05), with no change in MyHC type II fibers. Satellite cell content increased ~40% in both fiber types (P > 0.05). RET induced adaptations to the capillary supply to satellite cells, with the distance between satellite cells and the nearest capillary increasing in type I fibers and decreasing in type II fibers. Both fiber types showed similar decrements in intramuscular lipid density with training (P < 0.05). Our data provide intriguing evidence for a fiber type-specific response to RET in older adults and suggest flexibility in the myonuclear domain of type II fibers during a hypertrophic stimulus.NEW & NOTEWORTHY In older adults, progressive resistance exercise training (RET) increased skeletal muscle fiber volume and cross-sectional area independently of myonuclear accretion, leading to an expansion of the myonuclear domain. Fiber type-specific analyses illuminated differential adaptation; type II fibers underwent hypertrophy and exhibited myonuclear domain plasticity, whereas myonuclear accretion occurred in type I fibers in the absence of a robust hypertrophic response. RET also augmented satellite cell-capillary interaction and reduced intramyocellular lipid density to improve muscle quality.

CONDITION OF INTRACARDIAC HEMODYNAMICS AND MICROCIRCULATION IN PATIENTS WITH CHRONIC ISCHEMIC HEART DISEASE AND CONCOMITANT DIFFUSE LIVER DISEASES

&#x0D; &#x0D; &#x0D; Introduction. It is known that patients with ischemic heart diseases have endothelial dysfunction, but there is lack of research about microcirculation in these patients with diffuse liver diseases, especially diagnosed with digital capillaroscopy. Aim. To investigate hemodynamic disorders and microcirculation in patients with chronic ischemic heart disease depending on the presence of diffuse liver diseases and its severity with the digital capillaroscopy. Materials and methods. Our prospective study included 187 patients according to the criteria of inclusion. The data of echocardiography and digital capillaroscopy were analysed. Results. In our research in patients with ejection fraction less than 40% there was revealed thickening of the wall of the left ventricle, low blood supply in arterial and venous parts of capillaries. Patients with ejection fraction less than 40% and progressive diffuse liver diseases had advanced thickening of the wall of the left ventricle. Patients with liver cirrhosis had more adverse changes in hemodynamics. Patients with ischemic heart disease and diffuse liver disease had the worst capillary blood supply. Patients with ejection fraction less than 40% and diffuse liver diseases had structural changes of capillaries such as bi-, trifurcation and bushy forms. Conclusions. So, diffuse liver diseases, especially severe, cause endothelial dysfunction in patients with ischemic heart diseases. Digital capillaroscopy is a noninvasive method for microcirculation diagnosis and patients’ monitoring.&#x0D; &#x0D; &#x0D;

Capillary facilitation of skeletal muscle function in health and disease.

Skeletal muscle is highly vascularized, with perfusion being tightly regulated to meet wide-ranging metabolic demands. For decades, the capillary supply has been explored mainly in terms of evaluating the capillary numbers and their function in the supply of oxygen and substrates and the removal of metabolic byproducts. This review will focus on recent discoveries concerning the role played by capillaries in facilitating other aspects of cell regulation and maintenance, in health and disease, as well as alterations during the aging process. Novelty Capillaries play a central role in the coordination of the vascular response that controls blood flow during contraction and the cellular responses to which they feed into. Nitric oxide is an important regulatory compound within the cardiovascular system, and a significant contributor to skeletal muscle capillary angiogenesis and vasodilatory response to agonists. The microvascular network between muscle fibres may play a critical role in the distribution of signalling factors necessary for optimal muscle satellite cell function.

The distribution of Preputial vessels in different severity of rat congenital hypospadias model: imaging study using micro-computerized tomography

BackgroundMicro-computerized tomography (micro-CT) is considered as an innovative non-invasive and high-resolution imaging technology. The current research aims to reconstruct the distribution of preputial vessels in different severity of rat congenital hypospadias model by micro-CT, and to provide an anatomic basis for the selection of preputial vessel pedicle flaps in surgery.MethodsPregnant rats were exposed to finasteride from gestational day 12 to 17. Depending on the position of the urethral meatus, the pups were divided into normal, mild hypospadias and severe hypospadias groups. Six months after birth, the preputial blood vessels were observed in vascular perfusion with Microfil (a silicone-based polymer) and scanned by micro-CT. CTvox and NRecon were utilized to reconstruct 3-dimentional (3D) images. A pathological analysis of the specimen was taken in order to determine the position of Microfil.ResultsThe normal group and the mild hypospadias group had similar preputial image characteristics. At the junction of the inner and outer prepuce, the deep layer vessels of the superficial fascia were transversely distributed and formed a vascular ring-like structure. Among the severe hypospadias group, five had sufficient blood circulation while six had insufficient blood circulation. In sufficient blood circulation type, the ring-like vessels were found at the junction of the inner and outer prepuce similar to that of the normal and mild hypospadias group. However, only a small amount of capillary supply to this area in the insufficient type.ConclusionThe junction of the inner and outer prepuce with abundant blood circulation was suitable to be a vascular pedicle flap. The tubularized preputial island flaps were consistent with the ring-like vessels area, and the original blood supply was retained to the greatest extent.