Ylva Hellsten

University of Copenhagen · Department of Nutrition, Exercise and Sports

The risk of cardiovascular disease increases significantly after menopause. We sought to assess the impact of different activity levels on cardiac structure and function in postmenopausal women. We grouped age‐similar, postmenopausal women by self‐reported physical activity levels over two decades. The study involved 34 women (age 61 ± 1 years; 11...

This study investigated the effects of 14 days low energy availability (LEA) versus optimal energy availability (OEA) in endurance‐trained females on substrate utilization, insulin sensitivity, and skeletal muscle mitochondrial oxidative capacity; and the impact of metabolic changes on exercise performance. Twelve endurance‐trained females (V̇O2max...

In the Greenlandic Inuit population, 4% are homozygous carriers of a genetic nonsense TBC1D4 p.Arg684Ter variant leading to loss of the muscle-specific isoform of TBC1D4 and an approximately tenfold increased risk of type 2 diabetes¹. Here we show the metabolic consequences of this variant in four female and four male homozygous carriers and matche...

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 n...

301 words) 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...

Objective: The menopausal transition, marked by the cessation of endogenous estrogen production, is a hallmark of vascular aging in women, as the vascular function radically declines in the years hereafter (Parker et al. 2010). Primarily based on animal and in-vitro studies (Novella et al. 2012; Novensà et al. 2011; Park et al. 2017) it has been hy...

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 (V̇O 2max : 68.3 ±...

Purpose Short periods of reduced energy availability are commonly undertaken by athletes to decrease body mass, possibly improve the power-to-mass ratio, and enhance physical performance. Our primary aim was to investigate the impact of 10 days of low energy availability (LEA) followed by 2 days of optimal energy availability (OEA) on physical perf...

We showed an association between atrial fibrillation and rare loss-of-function (LOF) variants in the cardiac splicing regulator RBM20 in 2 independent cohorts. In a rat model with loss of RBM20, we demonstrated altered splicing of sarcomere genes (NEXN, TTN, TPM1, MYOM1, and LDB3), and differential expression in key cardiac genes. We identified alt...

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 di...

Aim: Histidine-containing dipeptides (HCDs) are pleiotropic homeostatic molecules with potent antioxidative and carbonyl quenching properties linked to various inflammatory, metabolic, and neurological diseases, as well as exercise performance. However, the distribution and metabolism of HCDs across tissues and species are still unclear. Methods:...

Although regular physical activity is known to improve cardiovascular health in men, evidence for its beneficial effects in postmenopausal females is less convincing and it remains unclear whether initiation of exercise training soon after, rather than many years after menopause impacts the magnitude of training-induced adaptations. We evaluated ex...

Aims The aim of this study is to examine whether colchicine improves β adrenoceptor‐mediated vasodilation in humans by conducting a double‐blinded, placebo‐controlled intervention study. Colchicine treatment has known beneficial effects on cardiovascular health and reduces the incidence of cardiovascular disease. Studies in isolated rodent arteries...

Histidine-containing dipeptides (HCDs) are pleiotropic homeostatic molecules linked to inflammatory, metabolic and neurological diseases, as well as exercise performance. Using a sensitive UHPLC-MS/MS approach and an optimized quantification method, we performed a systematic and extensive profiling of HCDs in the mouse, rat, and human body (in n=26...

Exercise-induced skeletal muscle angiogenesis is a well-known physiological adaptation that occurs in humans in response to exercise training and can lead to endurance performance benefits, as well as improvements in cardiovascular and skeletal tissue health. An increase in capillary density in skeletal muscle improves diffusive oxygen exchange and...

Although ageing impairs cardiovascular health in both men and women, the timeline is different between the sexes. This is at least partially attributed to the loss of oestrogen in women at midlife, in connection with menopause. Oestrogen has protective effects on the cardiovascular system, and menopause consequently leads to a rapid and significant...

The risk of thrombotic events dramatically increases with age and may be accelerated in women by the cessation of endogenous estrogen production at menopause. Patients at risk of thrombosis are prescribed dual anti-platelet therapy (DAPT; aspirin and a P2Y12 antagonist) and are encouraged to participate in regular physical activity, as these modali...

Aims: Colchicine treatment has known beneficial effects on cardiovascular health and reduces the incidence of cardiovascular disease. Studies in isolated rodent arteries have shown that colchicine can enhance β-adrenoceptor-mediated vasodilation. In this translational study we examined whether this effect of colchicine was present in humans by cond...

Background: The voltage-gated potassium channel (Kv)7.4 and Kv7.5 channels contribute to the β-adrenoceptor-mediated vasodilatation. In arteries from hypertensive rodents, the Kv7.4 channel is downregulated and function attenuated, which contributes to the reduced β-adrenoceptor-mediated vasodilatation observed in these arteries. Recently, we show...

Metformin is an inexpensive oral anti-hyperglycemic agent used worldwide as a first-choice drug for the prevention of type 2 diabetes mellitus (T2DM). Although current view suggests that metformin exerts its anti-hyperglycemic effect by lowering hepatic glucose production, it has been proposed that metformin also reduce hyperglycemia by increasing...

Purpose: To investigate the effect of intensity and duration of continuous and interval exercise training on capillarization in skeletal muscle of healthy adults. Methods: PubMed and Web of Science were searched from inception to June 2021. Eligibility criteria for studies were: endurance exercise training >2 wks in healthy adults, and capillary...

Introduction: Regular exercise training reduces arterial blood pressure but the underlying mechanisms are unclear. Here, we evaluated the potential involvement of Pannexin-1, an ATP releasing channel, in the blood pressure-reducing effect of training. Methods: Middle-aged men; 13 normotensive and 14 non-medicated stage 1 hypertensive, completed...

Background In preclinical models, the pannexin-1 channel has been shown to be involved in blood pressure regulation through an effect on peripheral vascular resistance. Pannexin-1 releases ATP, which can activate constrictive purinergic receptors on the smooth muscle cells. Pannexin-1 opening is proposed to be mediated by α-adrenergic receptors to...

The decline in estrogen at menopause poses a critical challenge to cardiovascular and metabolic health. Recently, a growing interest in the role of phytoestrogens, with a particular focus on isoflavones, has emerged as they can bind to estrogen receptors and may mimic the roles of endogenous estrogen. Fermented red clover extract (RC) contains isof...

The vasoconstrictive effect of sympathetic activity is attenuated in contracting skeletal muscle (functional sympatholysis), allowing increased blood supply to the working muscle but the underlying mechanisms are incompletely understood. The purpose of this study was to examine α-adrenergic receptor responsiveness in isolated artery segments from n...

Aerobic training can improve vascular endothelial function in-vivo. The aim of this study was to elucidate the mechanisms underlying this improvement in isolated human microvascular endothelial cells. Sedentary males, aged 57 ± 6 years completed 8 weeks of intense aerobic training. Resting muscle biopsies were obtained from the thigh muscle and use...

Rationale: In women, the risk of coronary heart disease increases significantly after the onsetof menopause. Exercise and active lifestyle have known benefits such as a significantly reducedrisk of heart failure. To date, most of the knowledge on physical activity induced changes incardiac function in older individuals are based on males and with a...

The influence of glucose and palmitic acid (PA) on mitochondrial respiration and emission of hydrogen peroxide (H2 O2 ) was determined in skeletal muscle-derived microvascular endothelial cells. Measurements were assessed in intact and permeabilized (cells treated with 0.025% saponin) low passage endothelial cells with acute-or prolonged (3 days) i...

The influence of the menopausal transition, with a consequent loss of oestrogen, on capillary growth in response to exercise training remains unknown. In the present study, we evaluated the effect of a period of intense endurance training on skeletal muscle angiogenesis in late pre-menopausal and recently post-menopausal women with an age differenc...

Key points Tamoxifen‐inducible skeletal muscle‐specific AXIN1 knockout (AXIN1 imKO) in mouse does not affect whole‐body energy substrate metabolism. AXIN1 imKO does not affect AICAR or insulin‐stimulated glucose uptake in adult skeletal muscle. AXIN1 imKO does not affect adult skeletal muscle AMPK or mTORC1 signalling during AICAR/insulin/amino aci...

Purpose: This study aimed to evaluate the influence of lifelong regular physical activity on skeletal muscle capillarization in women. Methods: Postmenopausal women, 61±4 yr old, were divided according to self-reported physical activity level over the past 20 yrs: sedentary (SED; n = 14), moderately active (MOD; n = 12), and very active (VERY; n...

Exercise training is a powerful strategy to prevent and combat cardiovascular and metabolic diseases, although the integrative nature of the training-induced adaptations is not completely understood. We show that chronic blockade of histamine H 1 /H 2 receptors led to marked impairments of microvascular and mitochondrial adaptations to interval tra...

The aim of this study was to determine the effect of a period of aerobic high intensity training on central- and peripheral cardiovascular parameters in older post-menopausal women. Eleven healthy post-menopausal (>10 years after menopause) women (mean age: 64 years; BMI: 25.3 kg m−2) completed an 8-week period of supervised, high intensity cycle t...

Purpose: Skeletal muscle vascularization is important for tissue regeneration after injury and immobilization. We examined whether complete immobilization influences capillarization and oxygen delivery to the muscle and assessed the efficacy of rehabilitation by aerobic exercise training. Methods: Young healthy males had one leg immobilized for...

Arterial thrombosis is the primary cause of death worldwide, with the most important risk factors being smoking, unhealthy diet, and physical inactivity. However, although there are clear indications in the literature of beneficial effects of physical activity in lowering the risk of cardiovascular events, exercise can be considered a double-edged...

In 1998, Norman Kaplan wrote in an editorial in the American Journal of Hypertension: “The measurement of blood pressure is likely the clinical procedure of greatest importance that is performed in the sloppiest manner” ¹– a statement which still is highly relevant.

BACKGROUND The mechanisms underlying the effect of preconditioning on remote microvasculature remains undisclosed. The primary objective was to document the remote effect of ischemic preconditioning on microvascular function in humans. The secondary objective was to test if exercise also induces remote microvascular effects. METHODS AND RESULTS A...

The menopausal transition is accompanied by changes in adipose tissue storage, leading to an android body composition associated with increased risk of type 2 diabetes and cardiovascular disease in post-menopausal women. Estrogens probably affect local adipose tissue depots differently. We investigated how menopausal status and exercise training in...

Angiogenic‐, mitochondrial‐ and related transcriptional proteins were assessed in human skeletal muscle and isolated vascular cells during the early phase of endurance training. Thigh muscle biopsies were obtained in healthy young subjects, after one acute bout (n=9) and after 3, 5, 7 and 14 days (n=9) of cycle ergometer training. Whole muscle homo...

Purpose: We examined whether two weeks of one-leg immobilization would impair leg microvascular function and to what extent a subsequent period of intense aerobic cycle training could restore function. Methods: Study participants were healthy young males (n=12; 20-24 years of age). Leg microvascular function was determined before the interventio...

Purpose: Remote ischaemic preconditioning (RIPC) refers to the protection conferred to tissues and organs via brief periods of ischaemia in a remote vascular territory, including the brain. Recent studies in humans report that RIPC provides neuroprotection against recurrent (ischaemic) stroke. To better understand the ability of RIPC to improve br...

Key points Increased insulin action is an important component of the health benefits of exercise, but its regulation is complex and not fully elucidated. Previous studies of insulin‐stimulated GLUT4 translocation to the skeletal muscle membrane found insufficient increases to explain the increases in glucose uptake. By determination of leg glucose...

Introduction: The study evaluated the role of life-long physical activity for leg vascular function in post-menopausal women (61±1 years). Method: The study design was cross-sectional with 3 different groups based on their self-reported physical activity level with regard to intensity and volume over the past decade: Inactive (n=14); Moderately...

Background: Remote ischaemic preconditioning (rIPC) may improve cardiac/cerebrovascular outcomes of ischaemic events. Ischaemic damage caused by cardiovascular/cerebrovascular disease are primary causes of mortality in type 2 diabetes mellitus (T2DM). Due to the positive effects from a bout of rIPC within the vasculature, we explored if daily rIPC...

Traumatic strain injury in skeletal muscle is often associated with fluid accumulation at the site of rupture, but the role of this injury exudate (EX) in cellular responses and healing is unknown. We aimed to characterize the EX sampled from human hamstring or calf muscles following a strain injury (n = 12). The cytokine and growth‐factor profile,...

The study examined the effect of 8 weeks of exercise training on ATP signalling in human skeletal muscle of 15 young (25±1 years) and 15 older (72±1 years) recreationally active male subjects. Before training, femoral venous plasma [ATP] was higher (P<0.05) during low‐intensity knee‐extensor exercise in the older than the young group. During modera...

Background: We examined the influence of recent menopause and aerobic exercise training in women on myocardial perfusion, left ventricular (LV) dimension and function. Methods: Two groups (n=14 each) of healthy late pre- (50.2±2.1 years) and recent postmenopausal (54.2±2.8 years) women underwent cardiac magnetic resonance imaging (cMRI) at basel...

Aims/hypothesis Plasma ATP is a potent vasodilator and is thought to play a role in the local regulation of blood flow. Type 2 diabetes is associated with reduced tissue perfusion. We aimed to examine whether individuals with type 2 diabetes have reduced plasma ATP concentrations compared with healthy control participants (case–control design). Me...

From 19th to 22nd November 2018, 26 researchers representing nine countries and a variety of academic disciplines met in Snekkersten, Denmark, to reach evidence-based consensus about physical activity and older adults. It was recognised that the term ‘older adults’ represents a highly heterogeneous population. It encompasses those that remain highl...

Type 2 diabetes is associated with microvascular dysfunction, but little is known about how capillary ultrastructure is affected by exercise training. To investigate the effect of two types of exercise training on skeletal muscle capillary ultrastructure and capillarization in individuals with type 2 diabetes, 21 individuals with type 2 diabetes we...

Aim: The aim was to determine the role of aging and exercise training on endothelial mechanosensor proteins and the hyperemic response to shear stress by passive leg movement. Methods: We examined the expression of mechanosensor proteins and vascular function in young (n = 14, 25 ± 3 years) and old (n = 14, 72 ± 5 years) healthy male subjects with...

Objective: The axis of apolipoprotein M (apoM) and sphingosine-1-phosphate (S1P) is of importance to plasma lipid levels, endothelial function, and development of atherosclerosis. Menopause is accompanied by dyslipidemia and an increased risk of atherosclerosis, which can be lowered by exercise training. The aim of this study was to explore if eff...

Objective The relationship between skeletal muscle perfusion, interstitial glucose concentration and sarcolemmal permeability to glucose in exercise-induced increases in muscle insulin sensitivity is not well established. A single bout of exercise increases skeletal muscle insulin sensitivity through coordinated increases in insulin-stimulated micr...

This study compared the effects of moderate-intensity endurance training and high-intensity interval training on fiber type-specific subcellular volumetric content and morphology of lipid droplets and mitochondria in skeletal muscles of type 2 diabetic patients. Sixteen sedentary type 2 diabetic patients (57{plus minus}7 years old) were randomized...

Background ATP is a potent vasodilator in plasma and is released from erythrocytes upon deoxygenation. In vitro studies suggest that individuals with type 2 diabetes (T2D) have an impaired ATP release when exposed to low oxygen tension and a reduced capability to induce vasodilation. We sought to examine if patients with T2D have reduced plasma ATP...

The aim of this study was to investigate the levels of motivation associated with participation in floorball (indoor hockey) and spinning, and how levels of motivation predicted continuation. A sample of 66 middle-aged women participated in a 12-week intervention of either floorball or spinning. They filled out the Sport Motivation Scale in week 2...

Background: The risk of atherothrombotic events increases after menopause. Regular physical activity has been shown to reduce platelet reactivity in younger women, but it is unknown how regular exercise affects platelet function after menopause. Objectives: To examine the effects of regular aerobic exercise in late pre- and recent postmenopausal...

Purpose: Animal studies suggest that the inhibition of nitric oxide synthase (NOS) affects blood flow differently in different skeletal muscles according to their muscle fibre type composition (oxidative vs glycolytic). Quadriceps femoris (QF) muscle consists of four different muscle parts: vastus intermedius (VI), rectus femoris (RF), vastus medi...

Menopause is associated with a decline in vascular function; however, whether this is an effect of age and/or menopause and the mechanisms underlying this decline remains unclear. We examined the vascular response to femoral arterial infusion of vasoactive compounds in 20 pre‐and 17 recent postmenopausal women of similar age (49±2 vs. 53±2 years)....

Aging is associated with impaired blood flow regulation; however, the mechanisms underlying this impairment and to what extent a period of exercise training can improve the matching between O 2 delivery and utilization remain unclear. Eight young and 6 older (24 ± 1 vs. 74 ±2 years) healthy sedentary men participated in the study. We examined the v...