It has been hypothesized that age‑related declines in skeletal muscle and vascular function in females may be partly estrogen‑dependent. This study investigated skeletal muscle protein expression of estrogen receptor α (ERα), estrogen receptor β (ERβ), and G protein–coupled estrogen receptor 1 (GPER1), and their association with proteins involved in redox regulation and vascular function, in relation to age, menopausal status, and lifelong physical activity. Skeletal muscle biopsies were obtained from 107 healthy females aged 19–70 years, including 26 postmenopausal females who were lifelong exercise trained. Protein expression of ERα, ERβ, GPER1, and downstream redox‑ and vascular‑related proteins was quantified. Age‑ and menopause‑related differences, associations between protein targets, and effects of lifelong exercise were examined. ERα protein expression was lower in older females with a 48

Background Cardiovascular disease risk accelerates in women after the menopausal transition, coinciding with the cessation of endogenous oestrogen production. The accompanying decline in vascular function is considered a key driver of this shift. However, longitudinal studies investigating the impact and time course of changes in cardiovascular and skeletal muscle function during the menopausal transition and in the subsequent years are warranted.Objectives The Women in Healthy Transition (KiSO) Deep Phenotyping (DP) study is a multidisciplinary prospective longitudinal cohort study with the objective to determine cardiovascular changes from the late reproductive stage through 20 years of postmenopause. The primary outcome is quantification of endothelium-dependent vascular function. Secondary outcomes include evaluating endothelium-independent vascular function, conduit artery endothelial function, mitochondrial function, circulating skeletal muscle vascular markers and sociological factors. The overall aim is to provide deep mechanistic, longitudinal insight into menopause-related vascular ageing to inform future cardiovascular disease prevention strategies in women.Methods 200 healthy women will be examined at the late reproductive stage and at 1, 3, 5, 10 and 20 years postmenopause. At each test round vascular function is evaluated using invasive intra-arterial infusion protocols, including acetylcholine and epoprostenol infusions, as well as flow-mediated dilation. Additional measures include arterial blood pressure, arterial compliance, echocardiography, cardiorespiratory fitness, whole-blood rheology, dual-energy X-ray absorptiometry-derived body composition, circulating reproductive and cardiometabolic biomarkers, skeletal muscle biopsies for assessment of mitochondrial capacity and proteins related to skeletal muscle and cardiometabolic health. Menopausal staging is determined using Stages of Reproductive Aging Workshop (STRAW)+10 criteria supported by follicle-stimulating hormone, anti-Müllerian hormone concentrations and antral follicle count.Ethics and dissemination The study is conducted in accordance with the Declaration of Helsinki and has been approved by the regional ethics committee: Ethics Committee of Copenhagen (H-22025286) and is registered with ClinicalTrial.gov (NCT05647876). Findings from the study will be disseminated through publications in peer-reviewed scientific journals, presentations at national and international conferences and through PhD theses. The results are expected to provide novel insights into the development of vascular and skeletal muscle function across the menopausal transition and may contribute to future strategies for prevention of cardiovascular disease in women.Trial registration number NCT05647876.

Cardiovascular control during exercise is impaired in chronic obstructive pulmonary disease (COPD). The central cardiopulmonary pathologies in COPD might drive the local muscle vascular abnormalities. We hypothesised that contracting muscle perfusion and O2 utilisation improve after lung transplantation (LTx) in COPD. Ten patients with end-stage COPD were tested on the LTx waiting list (pre-LTx) and again 6 months after LTx (post-LTx). We measured leg blood flow ( Q ̇ leg , main outcome) during submaximal one-leg knee-extensor exercise (KEE), and femoral arterial-venous blood samples were obtained for the determination of O2 kinetics across the leg and vasoactive compounds. Cardiac output and stroke volume in response to KEE peak workload (WLpeak), walking distance and physical activity (triaxial accelerometry) were also assessed. Lung function (one single and nine double LTx), walking distance and physical activity increased post-LTx, whereas leg lean mass and WLpeak remained unchanged. Arterial oxygen partial pressure decreased in response to KEE pre-LTx but was maintained at resting levels post-LTx. Working muscle capillary O2 tension and saturation were also higher post-LTx, with no difference in muscle O2 conductance or extraction. We found no changes in Q ̇ leg during submaximal KEE (pre-LTx: 1026 ± 278 vs. post-LTx: 941 ± 186 mL min-1, P = 0.49); mean arterial pressure and circulating pro-brain natriuretic peptide levels were lower post-LTx and cardiac output higher. Cardiac output (pre-LTx: 6.1 ± 0.4 vs. post-LTx: 8.3 ± 0.5 L min-1, P = 0.0001) and stroke volume responses to WLpeak were also higher post-LTx. LTx did not affect muscle blood flow regulation during moderate-intensity KEE in end-stage COPD and seemed to be disconnected from the augmented cardiac output responses to exercise.

Mitochondrial-derived peptides are a small class of regulatory peptides encoded by short open reading frames in mitochondrial DNA. One such peptide, mitochondrial open reading frame of the 12S rRNA-c (MOTS-c), has been shown to exert numerous beneficial effects on whole-cell and systemic metabolic parameters when administered exogenously. However, potential MOTS-c-mediated effects on mitochondrial bioenergetics have been largely overlooked. Therefore, the primary aim of the present study was to elucidate whether and, if so, how MOTS-c regulates skeletal muscle (SkM) mitochondrial function. We demonstrate, using two distinct transgenic mouse strains, that administration of MOTS-c augments muscle mitochondrial bioenergetic performance through reliance on both the transcriptional coactivator, Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), and cellular energy-sensing kinase, 5' adenosine monophosphate-activated protein kinase (AMPK). These effects seem to be exerted without apparent impact on mitochondrial respiratory protein content, alluding to intrinsic mitochondrial changes rather than changes in volume. Furthermore, MOTS-c treatment lowers mitochondrial reactive oxygen species (ROS) emission and ROS-related protein damage indicating substantial alleviation of cellular oxidative stress. RNA-sequence data reveal the effects of MOTS-c treatment to potentially be exerted subtly across a number of mitochondrial parameters such as redox handling, mitochondrial integrity and OXPHOS efficiency, jointly indicating a mechanistic basis for the observed functional improvements in mitochondrial bioenergetics. Despite increased interstitial MOTS-c levels no change was observed in the arterio-venous difference during one-legged knee extensor exercise in humans. This suggests that SkM may not be the source of circulating MOTS-c in response to exercise.

Exercise in healthy individuals is associated with a hypercoagulable phase, leading to a temporary increase in clot mass and strength, which are controlled by an effective fibrinolytic system. Conversely, people with cardiovascular diseases often have a reduced fibrinolytic pathway, increased clot mass and abnormal clot contraction, resulting in poorer outcomes. We assessed clot microstructure, particularly the contractile forces of clot formation, in response to two exercise intensities in middle-aged/older runners. Twenty-eight habitual male and female runners aged over 40 years completed a 10 km moderate-intensity run; 14 of them performed a 3 km high-intensity run. Blood samples were collected at baseline, immediately postexercise and after 1 h of rest. Clot structural biomarkers df, gel time, and measurements of mature clot mechanical properties (gel time, G’Max and CFmax) were analysed alongside conventional plasma markers. Both exercise intensities altered markers of coagulant activity (PT, APTT and FVIII) and fibrinolysis (D-dimer), indicating hypercoagulability. Compared with longer-duration lower-intensity exercise, df was greater after short-duration intensified exercise bouts. Following an hour of rest, df dropped to baseline levels. Additionally, CFmax decreased across timepoints at both exercise intensities. This effect was noted after one hour of rest compared with baseline, suggesting continuous fibrinolytic activity postexercise. Exercise transiently induces an intensity-dependent hypercoagulable state, resulting in denser clot formation and a reduced clot contractile force due to fibrinolysis. These findings can help guide the safe commencement of rehabilitation exercise programs for cerebrovascular patients.

In this review, we hypothesize that delaying physical training initiation until several years after menopause reduces the benefits of exercise on muscle function and cardiovascular health. Early engagement in exercise may counteract the negative effects of estradiol loss by activating pathways with similar molecular targets as estrogen, thereby helping to preserve muscle function and cardiovascular health during the postmenopausal period.

Many athletes and coaches believe that reducing body mass can improve the power-to-body mass ratio and improve exercise performance. This narrative review aims to characterize the effects of short-term (days to weeks) severe (< 30 kcal/kg Fat Free Mass/day) low energy availability (LEA) on exercise performance and physiological parameters related to health and training adaptations in female athletes. The latter is based on the prevalence of LEA being higher among female athletes, and most of the research is conducted on this population. In addition, we briefly address emerging evidence on short-term severe LEA in male athletes to highlight potential sex differences in physiological responses and performance outcomes. Short-term severe LEA triggers energy-conserving responses, leading to disruption in several crucial physiological systems, including suppression of the hypothalamic-pituitary-ovarian axis, decrease in triiodothyronine and insulin-like growth factor I hormones, reduction in resting metabolic rate, and comprised protein turnover in collagen-rich tissues. If these detrimental effects of short-term severe LEA are not reversed, they can progress to long-term problematic LEA, resulting in hypothalamic amenorrhea, lowering of bone mineral density, increased injury risk, and impaired exercise performance. Recent studies further underscore the detrimental impact of short-term severe LEA in female athletes, revealing suppressed muscle protein synthesis, increased cortisol levels, altered immune function, enhanced fat utilization during exercise, and direct impairments in power, sprinting, and endurance exercise performances despite reductions in body mass. These findings highlight the concerns about the trade-offs between short-term severe LEA for body mass reduction and the ability to maintain optimal physiological function for exercise performance. Further, they challenge the widespread assumption that body mass reduction always improves exercise performance, emphasizing a need for case-by-case considerations within the sporting environment.

The International Consensus Conference "Optimising Performance of the Elite Athlete," held in November 2024, brought together 29 scientists, some coaches, and athletes to establish evidence-based consensus statements aimed at enhancing elite athletic performance and health. The conference addressed critical themes including training strategies, nutrition, female athlete considerations, injury management, and emerging technologies. Key conclusions emphasize individualized, sport-specific approaches to training and nutrition, integrating concurrent training modalities to improve endurance, resilience, and efficiency. Nutrition strategies highlight the importance of tailored energy and macronutrient periodization, recognition of low energy availability risks, and cautious use of dietary supplements. Special attention was directed to female athletes, advocating for improved monitoring of menstrual cycles and hormonal status, while acknowledging current knowledge gaps in hormonal influences on performance and injury risk. Injury prevention remains a challenge, with tendon overuse and Achilles tendon ruptures significantly impacting athlete careers; rehabilitation should rely on criteria-based progression and multidisciplinary input. Emerging technologies, including wearable sensors and multi-omics analyses, hold promise for personalized training and nutrition but require further validation in elite contexts. Despite robust consensus, the panel identified substantial research gaps, particularly regarding female athletes, longitudinal training effects, and efficacy of novel interventions. This consensus provides a practical, scientifically grounded framework to optimize elite athlete performance and health, while underscoring the need for continued research to address outstanding questions and promote inclusive evidence-based practices.

Background:The study evaluated the effect of an acute and a 2-week daily repetitive ischemic preconditioning (IPC) on conduit artery vascular function and thrombogenic clotting profile, in patients with a recent ischemic stroke. Methods:Fourteen patients, aged 71 ± 8 years, with a cerebral small vessel occlusion stroke were included in a randomized, controlled, open-label cross-over study. Treatment consisted of 2 weeks of daily IPC, four 5-min rounds of upper-arm occlusion, interspersed by 5 min rest periods. Control was without treatment. Brachial artery flow-mediated dilation (FMD) was determined at baseline and after the control and treatment periods. Before and after each period, the patients underwent an acute bout of IPC. Blood samples were obtained for thrombogenic clotting profile at baseline and after the acute IPC bout, both before and after the control and treatment periods. Results:The period of daily IPC increased brachial artery diameter but did not influence FMD. Acutely, IPC was found to induce an increase in fractal dimension, indicating a denser clot microstructure, and a reduction in plasma levels of plasminogen activator inhibitor 1 (PAI-1). There was no effect of daily IPC on the basal thrombogenic clotting profile, or on the change in clotting profile induced by acute IPC. Conclusions:Collectively, the data show that acute IPC leads to a prothrombotic clotting profile, despite antiplatelet therapy. Moreover, 2 weeks of daily treatment with IPC does not influence conduit artery vascular function or thrombogenicity in stroke patients.

A single bout of exercise improves muscle insulin sensitivity for up to 48 hours via AMPK. Limb ischemia activates AMPK in muscle, and subsequent reperfusion enhances insulin-stimulated vasodilation, potentially eliciting a more pronounced exercise effect with reduced workload. We investigated the combined effect of upper leg intermittent ischemia/reperfusion (IIR) and continuous knee-extension exercise on muscle insulin sensitivity regulation. We found that IIR exercise potentiated AMPK activation and muscle insulin sensitivity. The potentiating effect of IIR exercise on muscle insulin sensitivity was associated with increased insulin-stimulated blood flow in parallel with enhanced phosphorylation of endothelial nitric oxide synthase. Metabolomics analyses demonstrated a suppression of muscle medium-chain acylcarnitines during IIR exercise, which correlated with insulin sensitivity and was consistent with findings in isolated rat muscle treated with decanoyl-l-carnitine. Collectively, combining IIR with low- to moderate-intensity exercise may represent a promising intervention to effectively enhance muscle insulin sensitivity. This approach could offer potential for mitigating muscle insulin resistance in clinical settings and among individuals with lower physical activity levels.

Introduction: The effects of low energy availability (LEA) on the immune system are poorly understood. This study examined the effects of 14 days of LEA on immune cell redox balance and inflammation at rest and in response to acute exercise, and exercise performance in female athletes. Methods: Twelve female endurance athletes (age: 26.8 +/- 3.4 yrs, maximum oxygen uptake ((V) over dotO(2max)): 55.2 +/- 5.1 mL x min(-1) x kg(-1)) were included in a randomized, single-blinded crossover study. They were allocated to begin with either 14 days of optimal energy availability diet (OEA, 52 +/- 2 kcal x kg fat free mass (FFM)(-1) x day(-1)) or LEA diet (22 +/- 2 kcal x kg FFM-1 x day(-1)), followed by 3 days of refueling (OEA) with maintained training volume. Peripheral blood mononuclear cells (PBMCs) were isolated, and plasma obtained at rest before and after each dietary period. The PBMCs were used for analysis of mitochondrial respiration and H2O2 emission and specific proteins. Exercise performance was assessed on cycle by a 20-min time trial and time to exhaustion at an intensity corresponding to similar to 110 % (V) over dotO(2max)). Results: LEA was associated with a 94 % (P = 0.003) increase in PBMC NADPH oxidase 2 protein content, and a 22 % (P = 0.013) increase in systemic cortisol. LEA also caused an alteration of several inflammatory related proteins (P < 0.05). Acute exercise augmented H2O2 emission in PBMCs (P < 0.001) following both OEA and LEA, but to a greater extent following LEA. LEA also reduced the mobilization of white blood cells with acute exercise. After LEA, performance was reduced in both exercise tests (P < 0.001), and the reduced time trial performance remained after the 3 days of refueling (P < 0.001). Conclusion: 14 days of LEA in female athletes increased cortisol levels and had a pronounced effect on the immune system, including increased capacity for ROS production, altered plasma inflammatory proteome and lowered exercise induced mobilization of leukocytes. Furthermore, LEA resulted in a sustained impairment in exercise performance.

While it is well-established that a period of interval training performed at near maximal effort, such as speed endurance training (SET), enhances intense exercise performance in well-trained individuals, less is known about its effect on cardiac morphology and function as well as blood volume. To investigate this, we subjected 12 Under-20 Danish national team ice hockey players (age 18 ± 1 years, mean ± SD) to 4 weeks of SET, consisting of 6-10 × 20 s skating bouts at maximal effort interspersed by 2 min of recovery conducted three times weekly. This was followed by 4 weeks of regular training (follow-up). We assessed resting cardiac function and dimensions using transthoracic echocardiography and quantified total blood volume with the carbon monoxide rebreathing technique at three time points: before SET, after SET and after the follow-up period. After SET, stroke volume had increased by 10 (2-18) mL (mean (95% CI)), left atrial end-diastolic volume by 10 (3-17) mL, and circumferential strain improved by 0.9%-points (1.7-0.1) (all P < 0.05). At follow-up, circumferential strain and left atrial end-diastolic volume were reverted to baseline levels, while stroke volume remained elevated. Blood volume and morphological parameters for the left ventricle, including mass and end-diastolic volume, did not change during the study. In conclusion, our findings demonstrate that a brief period of SET elicits beneficial central cardiac adaptations in elite ice hockey players independent of changes in blood volume.

Abstract Introduction Older individuals and, in particular, individuals at risk of recurrent stroke, may be susceptible to thrombosis when participating in exercise, however, this aspect has not been well investigated. Methods Clot microstructure and conventional markers of thrombotic risk were determined in twenty lacunar stroke patients and fifteen healthy age-matched controls before, immediately after and 1 h after a bout of moderate intensity cycling exercise. Data were analyzed using a linear mixed model approach. Results At rest, clot microstructure (1.69 ± 0.07 vs. 1.64 ± 0.05, corresponding to a difference of ~ 50% in normalized clot mass; p = 0.009) and thrombocyte count (73%; p < 0.0001) were higher, and activated partial thromboplastin time was lower (18%; p = 0.0001) in stroke patients compared to age-matched controls. Acute exercise increased thrombogenic markers similarly in the two groups: incipient clot microstructure (1.69 ± 0.07 vs. 1.74 ± 0.05; p = 0.0004 and 1.64 ± 0.05 vs. 1.71 ± 0.04; p < 0.0001, for stroke and controls respectively), plasma fibrinogen (12%; p < 0.0001 and 18%; p < 0.0001, for stroke and controls respectively) and the combined coagulation factors II, VII and X (p = 0.0001 and p < 0.0001, for stroke and controls respectively). Conclusion The results show that exercise transiently increases the risk of blood clot formation in both stroke patients and controls, however, due to the higher baseline thrombogenicity in stroke patients, the post exercise risk of forming blood clots may be higher in this group. Trial registration Registered at ClinicalTrials.gov (NCT03635177).

The present study examined and compared the impact of exercise training on redox and molecular properties of human microvascular endothelial cells derived from skeletal muscle biopsies from sedentary recent (RPF, ≤ 5 years as postmenopausal) and late (LPF, ≥ 10 years as postmenopausal) postmenopausal females. Resting skeletal muscle biopsies were obtained before and after 8 weeks of intense aerobic exercise training for isolation of microvascular endothelial cells and determination of skeletal muscle angiogenic proteins and capillarisation. The microvascular endothelial cells were analysed for mitochondrial respiration and production of reactive oxygen species (ROS), glycolysis and proteins related to vascular function, redox balance and oestrogen receptors. Exercise training led to a reduced endothelial cell ROS formation (∼50%; P = 0.009 and P = 0.020 for intact and permeabilized cells (state 3), respectively) in RPF only, with no effect on endothelial mitochondrial capacity in either group. Basal endothelial cell lactate formation was higher (7%; P = 0.028), indicating increased glycolysis, after compared to before the exercise training period in RPF only. Baseline endothelial G protein-coupled oestrogen receptor (P = 0.028) and muscle capillarisation (P = 0.028) was lower in LPF than in RPF. Muscle vascular endothelial growth factor protein was higher (32%; P = 0.002) following exercise training in LPF only. Exercise training did not influence endothelial cell proliferation or skeletal muscle capillarisation in either group, but the CD31 level in the muscle tissue, indicating endothelial cell content, was higher (>50%; P < 0.05) in both groups. In conclusion, 8 weeks of intense aerobic exercise training reduces ROS formation and enhances glycolysis in microvascular endothelial cells from RPF but does not induce skeletal muscle angiogenesis. KEY POINTS: Late postmenopausal females have been reported to achieve limited vascular adaptations to exercise training. There is a paucity of data on the effect of exercise training on isolated skeletal muscle microvascular endothelial cells (MMECs). In this study the formation of reactive oxygen species in MMECs was reduced and glycolysis increased after 8 weeks of aerobic exercise training in recent but not late postmenopausal females. Late postmenopausal females had lower levels of G protein-coupled oestrogen receptor in MMECs and lower skeletal muscle capillary density at baseline. Eight weeks of intense exercise training altered MMEC properties but did not induce skeletal muscle angiogenesis in postmenopausal females.

The significant morbidity and premature mortality of type 2 diabetes mellitus (T2DM) is largely associated with its cardiovascular consequences. Focus has long been on the arterial atheromatosis of DM giving rise to early stroke and myocardial infarctions, whereas less attention has been given to its non-ischemic cardiovascular consequences. Irrespective of ischemic changes, T2DM is associated with heart failure (HF) most commonly with preserved ejection fraction (HFpEF). Largely due to increasing population ages, hypertension, obesity and T2DM, HFpEF is becoming the most prevalent form of heart failure. Unfortunately, randomized controlled trials of HFpEF have largely been futile, and it now seems logical to address the important different phenotypes of HFpEF to understand their underlying pathophysiology. In the early phases, HFpEF is associated with a significantly impaired ability to increase cardiac output with exercise. The lowered cardiac output with exercise results from both cardiac and peripheral causes. T2DM is associated with left ventricular (LV) diastolic dysfunction based on LV hypertrophy with myocardial disperse fibrosis and significantly impaired ability for myocardial blood flow increments with exercise. T2DM is also associated with impaired ability for skeletal muscle vasodilation during exercise, and as is the case in the myocardium, such changes may be related to vascular rarefaction. The present review discusses the underlying phenotypical changes of the heart and peripheral vascular system and their importance for an adequate increase in cardiac output. Since many of the described cardiovascular changes with T2DM must be considered difficult to change if fully developed, it is suggested that patients with T2DM are early evaluated with respect to their cardiovascular compromise.

PURPOSE:We investigated the effects of low- and high-volume speed endurance training (SET), with a reduced training volume, on sprint ability, short- and long-term exercise capacity, muscle mitochondrial properties, ion transport proteins, and maximal enzyme activity in highly trained athletes. METHODS:Highly trained male cyclists (maximal oxygen consumption (V̇O 2max ): 68.3 ± 5.0 mL·min -1 ·kg -1 , n = 24) completed 6 wk of either low (SET-L; 6 × 30-s intervals, n = 8) or high (SET-H; 12 × 30-s intervals, n = 8) volume SET twice per week with a 30% reduction in training volume. A control group (CON; n = 8) maintained their training. Exercise performance was evaluated by i) 6-s sprinting, ii) a 4-min time trial, and iii) a 60-min preload at 60% V̇O 2max followed by a 20-min time trial. A biopsy of m. vastus lateralis was collected before and after the training intervention. RESULTS:In SET-L, 4-min time trial performance was improved ( P < 0.05) by 3.8%, with no change in SET-H and CON. Sprint ability, prolonged endurance exercise capacity, V̇O 2max , muscle mitochondrial respiratory capacity, maximal citrate synthase activity, fiber type-specific mitochondrial proteins (complexes I-V), and phosphofructokinase (PFK) content did not change in any of the groups. In SET-H, maximal activity of muscle PFK and abundance of Na + -K + pump-subunit α 1 , α 2 , β 1 , and phospholemman (FXYD1) were 20%, 50%, 19%, 24%, and 42% higher ( P < 0.05), respectively after compared with before the intervention, with no changes in SET-L or CON. CONCLUSIONS:Low SET volume combined with a reduced aerobic low- and moderate-intensity training volume does improve short-duration intense exercise performance and maintain sprinting ability, V̇O 2max , endurance exercise performance, and muscle oxidative capacity, whereas, high volume of SET seems necessary to upregulate muscle ion transporter content and maximal PFK activity in highly trained cyclists.

Sufficient delivery of oxygen and metabolic substrates, together with removal of waste products, are key elements of muscle performance. Capillaries are the primary site for this exchange in skeletal muscle and the degree of muscle capillarization affects diffusion conditions by influencing mean transit time, capillary surface area and diffusion distance. Muscle capillarization may thus represent a limiting factor for performance. Exercise training increases the number of capillaries per muscle fiber by about 10%-20% within a few weeks in untrained subjects, whereas capillary growth progresses more slowly in well-trained endurance athletes. Studies show that capillaries are tortuous, situated along and across the length of the fibers with an arrangement related to muscle fascicles. Although direct data is lacking, it is possible that years of training not only enhances capillary density but also optimizes the positioning of capillaries, to further improve the diffusion conditions. Muscle capillarization has been shown to increase oxygen extraction during exercise in humans, but direct evidence for a causal link between increased muscle capillarization and performance is scarce. This review covers current knowledge on the implications of muscle capillarization for oxygen and glucose uptake as well as performance. A brief overview of the process of capillary growth and of physical factors, inherent to exercise, which promote angiogenesis, provides the foundation for a discussion on how different training modalities may influence muscle capillary growth. Finally, we identify three areas for future research on the role of capillarization for exercise performance.