James M Hagberg

• University of Maryland, College Park

Repeated exposure to a high-fat meal triggers inflammation and oxidative stress, contributing to the onset of cardiometabolic diseases. Regular exercise prevents cardiometabolic diseases and a prior bout of acute endurance exercise can counteract the detrimental cardiovascular effects of a subsequent high-fat meal. Circulating microRNAs (ci-miRs) a...

Both aberrant vascular reactivity to acute cardiovascular stress and epigenetic mechanisms such as microRNA (miR) may underlie the increased propensity for African Americans (AA) to develop cardiovascular disease. This study assessed racial differences in acute induced endothelial inflammation and related miRs. Cultured human umbilical vein endothe...

Exercise training has various benefits on cardiovascular health, and circulating angiogenic cells have been proposed as executing these changes. Work from the late 1990s supported an important role of these circulating post-natal cells in contributing to the maintenance and repair of the endothelium and vasculature. It was later found that circulat...

Concentrations of different circulating microparticles (MPs) may have clinical and physiological relevance to cardiovascular disease pathologies. Purpose: To quantify plasma concentrations of CD31+/CD42b-, CD62E+, and CD34+ MPs across healthy individuals and those with coronary artery disease (CAD) or acute cardiovascular events (non-ST elevation...

Mechanisms underlying the protective effects of both habitual endurance exercise and the female sex on vascular function are incompletely understood. Blood-borne circulating factors, such as circulating microRNAs (ci-miRs), may partially explain these effects. Blood samples were obtained from young, healthy men and women who either habitually perfo...

High-intensity interval (HII) exercise elicits distinct vascular responses compared to a matched dose of moderate intensity continuous (MOD) exercise. However, the acute effects of HII compared to MOD exercise on arterial stiffness are incompletely understood. Circulating microRNAs (ci-miRs) may contribute to the vascular effects of exercise. We so...

Endothelial function typically exhibits a hormetic response to exercise. It is unknown whether endothelial damage occurs in response to acute exercise and could be a contributing mechanism. We sought to determine the effects of acute exercise on endothelial-derived circulating factors proposed to reflect endothelial integrity and activation. Ten yo...

Circulating microRNAs (ci-miRs) are post-transcriptional regulators of gene expression released by cells into blood or other biofluids. Acute and chronic exercise have been shown to alter the profile of ci-miRs. The past few years have seen an upsurge in research detailing the exercise responses of ci-miRs and investigating their utility as biomark...

Postmenopausal African American women are at elevated risk for metabolic syndrome (MetS), which predisposes them to cardiovascular disease and other chronic diseases. Circulating microRNAs (ci-miR) are potential mediators of cardiometabolic diseases also impacted by cardiorespiratory fitness (CRF) level. Using real-time quantitative PCR, we compare...

Autologous stem/progenitor cell‐based methods to restore blood flow and function to ischemic tissues are clinically appealing for the substantial proportion of the population with cardiovascular diseases. Early preclinical and case studies established the therapeutic potential of autologous cell therapies for neovascularization in ischemic tissues....

John O. Holloszy, as perhaps the world's preeminent exercise biochemist/physiologist, published >400 papers over his 50+ year career, and they have been cited >41,000 times. In 1965 Holloszy showed for the first time that exercise training in rodents resulted in a doubling of skeletal muscle mitochondria, ushering in a very active era of skeletal m...

Prolonged sitting increases the risk for cardiovascular disease. However, markers of vascular repair and damage such as circulating angiogenic cell (CAC) populations and microparticles (MP) have not been characterized with prolonged sitting or sitting with intermittent activity. PURPOSE: To examine the effects of 3h of sitting with or without calf...

Purpose: Aggressive play in professional soccer, punished by referees with fouls and cards, carries increased injury risk. We compared fouls and cards in the English Premier League (EPL) with the next three divisions of English soccer over 17 seasons (2000/01–2016/17), to determine whether previously observed differences with other top European lea...

Background and aims: GlycA is a relatively new biomarker for inflammation as well as cardiometabolic disease risk. However, the effect of exercise on GlycA is largely unknown. Therefore, the purpose of this study was to examine the effects of regular exercise on the inflammatory marker GlycA across seven studies and 14 exercise interventions. Met...

Current trends suggest professional soccer is becoming less aggressive, with England often argued to have the most aggressive of the top European leagues. The purpose of this study was to investigate differences in fouls and cards as indicators of aggressive play in the first divisions of England, France, Germany, Italy, and Spain over the past dec...

This study compared physiological data from an elite collegiate soccer player to that of his teammates over two seasons. The player of special interest (Player A) was the winner of the MAC Hermann trophy and was therefore considered the top player in NCAA division I soccer for each of the two seasons in which data was collected. Maximal oxygen cons...

MicroRNAs (miRNAs) are short, non-coding RNAs that influence biological processes by regulating gene expression post-transcriptionally. It was recently discovered that miRNAs are released into the circulation (ci-miRNAs) where they are highly stable and can act as intercellular messengers to affect physiological processes. This review provides a co...

New & noteworthy: S100A8 and S100A9 proteins in concentrations secreted by CD34(-)/CD31(+) circulating angiogenic cells (CACs) with impaired function reduce endothelial cell capillary-like network formation. These effects appear to be mediated by Toll-like receptor 4 and are absent with S100A8 and S100A9 in concentrations secreted by healthy CD34(...

Cardiovascular disease risk increases with age due, in part, to impaired endothelial function and decreased circulating angiogenic cell (CAC) number and function. We sought to determine if 10 days of aerobic exercise training improves endothelial function, CAC number, and intracellular redox balance in older sedentary adults. Eleven healthy subject...

Objective: Our goal was to examine the effects of regular endurance exercise on plasma GlycA levels, a novel NMR-derived biomarker of systemic inflammation. Methods: We examined NMR-derived plasma GlycA levels before and after 5-6 months of exercise training in 1,194 adults from four studies: APOE (N=104), DREW (N=298), GERS (N=78), HERITAGE (N=714...

Objective: The goal was to examine lipoprotein subclass responses to regular exercise as measured in 10 exercise interventions derived from six cohorts. Methods: Nuclear magnetic resonance spectroscopy was used to quantify average particle size, total and subclass concentrations of very low-density lipoprotein, low-density lipoprotein, and high-de...

We aimed to determine if chronic endurance exercise habits affected redox status and paracrine function of CD34+ and CD34-/CD31+ circulating angiogenic cells (CACs). Subjects were healthy, nonsmoking, men and women aged 18-35 yrs and categorized by chronic physical activity habits. Blood was drawn from each subject for isolation and culture of CD34...

OBJECTIVE: The goal was to examine lipoprotein subclass responses to regular exercise as measured in 10 exercise interventions derived from six cohorts. We hypothesized that regular exercise has beneficial effects on the overall lipoprotein subclass profile in previously sedentary adults. METHODS: NMR spectroscopy (LipoScience Inc., Raleigh, NC) wa...

Endurance exercise training can ameliorate many cardiovascular and metabolic disorders and attenuate responses to inflammatory stimuli. The purpose of this study was to determine whether the angiogenic and pro-inflammatory cytokine response to acute endurance exercise differs between endurance-trained and sedentary young men. Ten endurance-trained...

High-fat meal consumption alters the circulating cytokine profile and contributes to cardiometabolic diseases. A prior bout of exercise can ameliorate the triglyceride response to a high-fat meal, but the interactive effects of exercise and high-fat meals on cytokines that mediate cardiometabolic risk are not fully understood. We investigated the e...

PURPOSE To determine if a relationship exists between physical fitness and the ability of CD34+ or CD34−/CD31+ circulating angiogenic cells (CAC) to influence angiogenic function through paracrine activity. METHODS Peripheral blood was drawn from healthy inactive (n = 7), active (n = 10) and endurance‐trained (n = 7) men and women aged 25–39. Mono...

A small number of excellent papers on exercise genomics issues have been published in 2012. A new PYGM knockout mouse model will provide opportunities to investigate the exercise intolerance and very low activity level of people with McArdle disease. New reports on variants in ACTN3 and ACE have increased the level of uncertainty regarding their tr...

Unlabelled: We initiated a pilot study to investigate the effects of 8 wks of aerobic exercise training (ET) on insulin sensitivity and inflammatory markers in obese and insulin-resistant minority adolescents. Eleven morbidly obese (BMI 41.4 ± 1.8 kg/m2) minority adolescents were entered into a supervised ET intervention (~180 min/wk at 40-55%VO2P...

Chronic low-grade systemic inflammation plays a role in the development of cardiovascular (CV) disease. Habitual endurance exercise training reduces the risk of CV disease in part through anti-inflammatory mechanisms. The purpose of this study was to investigate the effects of age, endurance training status, and their interaction on pro-inflammator...

Background and aims: Inflammation plays a role in the development of cardiovascular disease (CVD). Elevated levels of the inflammatory marker, C-reactive protein (CRP), are cross-sectionally associated with traditional CVD risk factors and are being considered as an emerging CVD risk factor. In a secondary data analysis, we examined changes in CRP...

Type 2 diabetes mellitus (T2DM) is at virtually pandemic levels world-wide. Diabetes has been referred to as 'a geneticist's nightmare'. However, dramatic advances in our understanding of the genetics of T2DM have occurred in the past 5 years. While endurance exercise training and increased habitual physical activity levels have consistently been s...

Individuals differ in the response to regular exercise. Whether there are people who experience adverse changes in cardiovascular and diabetes risk factors has never been addressed. An adverse response is defined as an exercise-induced change that worsens a risk factor beyond measurement error and expected day-to-day variation. Sixty subjects were...

Detailed description of the six studies and the background material used to determine the technical error for fasting insulin. (DOCX)

We examined the effect of prior endurance exercise on plasma angiogenic cytokine responses to a high fat meal as these may contribute to pathologic angiogenesis in atherosclerosis. Blood samples were obtained from 10 healthy men at baseline and 4 h postprandial with or without ~50 min of endurance exercise at 70% of VO 2 max the day before. Plasma...

Aerobic exercise capacity is inversely related to CVD risk and all cause mortality. p53 plays a crucial role in mitochondrial DNA (mtDNA) maintenance, which is important for mitochondrial function and disease prevention. Here, we extend this concept and investigate whether the p53 codon 72 R/P polymorphism is associated with the adaptive response t...

Oxidative stress markers are novel factors shown to be related to cardiovascular (CVD) risk. We examined the effects of long-term exercise, age, and their interaction on plasma oxidized LDL (ox-LDL), nitrotyrosine, and myeloperoxidase (MPO) levels, all biomarkers of oxidative stress, and determined their association with plasma nitric oxide (NOx) l...

This review of the exercise genomics literature emphasizes the highest quality articles published in 2011. Given this emphasis on the best publications, only a small number of published articles are reviewed. One study found that physical activity levels were significantly lower in patients with mitochondrial DNA mutations compared with controls. A...

Our objective was to test the hypothesis that a common polymorphism in the hepatic lipase (HL) gene (LIPC -514C>T, rs1800588) influences aerobic exercise training-induced changes in TG, very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) through genotype-specific increases in lipoprotein lipase (LPL) activity and that sex may af...

We hypothesized that prior exercise would prevent postprandial lipaemia (PPL)-induced increases in intracellular reactive oxygen species (ROS) in three distinct circulating angiogenic cell (CAC) subpopulations. CD34(+), CD31(+)/CD14(-)/CD34(-), and CD31(+)/CD14(+)/CD34(-) CACs were isolated from blood samples obtained from 10 healthy men before and...

Insulin-like growth factor binding protein-1 (IGFBP-1) has metabolic effects throughout the body, and its expression is regulated in part by insulin. Circulating IGFBP-1 predicts development of cardiometabolic diseases in longitudinal studies, and low IGFBP-1 concentrations are associated with insulin resistance and consumption of a high-fat diet....

We investigated the influence of acute and chronic endurance exercise on levels of intracellular nitric oxide (NO), superoxide (O₂·⁻), and expression of genes regulating the balance between these free radicals in CD34⁺ and CD34⁻ peripheral blood mononuclear cells (PBMCs; isolated by immunomagnetic cell separation). Blood samples were obtained from...

It is generally accepted that if prediabetic individuals adopt healthy lifestyle habits, the progression to type 2 diabetes mellitus can be prevented or delayed. However, the role of exercise training independent of other lifestyle factors has not been determined. Furthermore, patients with type 2 diabetes mellitus have been shown to experience gre...

Cardiovascular disease (CVD) and CVD risk factors are highly heritable, and numerous lines of evidence indicate they have a strong genetic basis. While there is nothing known about the interactive effects of genetics and exercise training on CVD itself, there is at least some literature addressing their interactive effect on CVD risk factors. There...

This review of the exercise genomics literature emphasizes the strongest articles published in 2010 as defined by sample size, quality of phenotype measurements, quality of the exercise program or physical activity exposure, study design, adjustment for multiple testing, quality of genotyping, and other related study characteristics. One study on v...

Plasma lipoprotein-lipid and blood pressure (BP) profiles vary substantially among individuals, and their levels have generally been found to be moderately heritable (0.20–0.60). Candidate gene and genome-wide linkage and association studies have provided further evidence for a genetic basis for the variability in these cardiovascular (CV) disease...

As part of the insulin signalling pathway, Akt influences growth and metabolism. The AKT1 gene G205T (rs1130214) polymorphism has potential functional effects. Thus, we determined whether the G205T polymorphism influences metabolic variables and their responses to aerobic exercise training. Following dietary stabilization, healthy, sedentary, 50- t...

WITKOWSKI, S., N.T. JENKINS, and J.M. HAGBERG. Enhancing treatment for cardiovascular disease: exercise and circulating angiogenic cells. Exerc. Sport Sci. Rev., Vol. 39, No. 2, pp. 93-101, 2011. The discovery of circulating angiogenic cells (CAC) with cardiovascular regenerative potential has transformed our understanding of the health and mainten...

the T-786C polymorphism of the gene for endothelial nitric oxide synthase (eNOS) and superoxide anion production may reduce production and bioavailability of nitric oxide, affecting the degree of vasodilation. This effect can be reversed by exercise. to investigate the influence of aerobic training and T-786C polymorphism in the concentrations of n...

genetic studies have generally focused on clinical or pathological phenotypes, such as obesity and diabetes. Now accumulating evidence indicates that our behaviors also have a strong genetic basis! The data presented by Lightfoot et al. in this issue of the Journal of Applied Physiology ([6a][1])

Life scientists, especially those of us from a previous generation (or two), were trained to focus our efforts on generating large mean differences between groups or large changes with interventions while minimizing variability. The goal was to maximize effect size, thereby optimizing the chance of generating a statistically significant difference...

Oxidative stress markers may be novel factors contributing to cardiovascular (CVD) risk. The purpose of this study was to examine the effects of long-term exercise, age, and their interaction on the plasma levels of the oxidative stress markers oxidized LDL (ox-LDL), nitrotyrosine, and myeloperoxidase (MPO), and to investigate whether these levels...

An annual review publication of the most significant articles in exercise, fitness, and performance genomics begins with this article, which covers 2 yr, 2008 and 2009. The review emphasizes the strongest articles as defined by sample size, quality of phenotype measurements, quality of the exercise program or physical activity exposure, study desig...

Acute exercise and exercise training may influence putative endothelial progenitor cell (EPC) number and colony forming units (CFU-ECs), although the mechanisms remain unclear. This study examined the effects of in vitro thrombin supplementation and acute exercise on CFU-EC gene expression, associated with cellular proliferation and differentiation...

Fetuin-A is a liver-derived factor that may play a role in insulin resistance and age-related chronic diseases (eg, type 2 diabetes mellitus and cardiovascular [CV] disease). Regular exercise improves CV risk and insulin sensitivity; however, it is unknown whether chronic exercise training is related to circulating levels of fetuin-A. Therefore, th...

Exercise may contribute to the maintenance of vascular function via enhanced liberation and action of bone-marrow-derived progenitor cells. Activity related changes in oxidative stress may also influence the number and function of these cells. In the present study, we sought to determine (i) whether adaptations in reactive hyperaemic FBF (forearm b...

Reduced nitric oxide (NO) production and bioactivity is a major contributor to endothelial dysfunction. Animal data suggest that improvements in endothelial function in response to aerobic exercise training may depend on the duration of the training program. However, no studies have examined changes in NO (as assessed by the major NO metabolites, n...

We sought to delineate the effects of acute and chronic exercise on the regulation of intracellular nitric oxide (NO(i)) production in putative endothelial progenitor cells (EPCs). Putative EPC colony-forming units (CFU-EC) were cultured from blood drawn before and after 30 min of treadmill exercise at 75% of maximal oxygen uptake in active (n = 8)...

Oxidative stress that is mediated through NADPH oxidase activity plays a role in the pathology of hypertension, and aerobic exercise training reduces NADPH oxidase activity. The involvement of genetic variation in the p22phox (CYBA) subunit genes in individual oxidative stress responses to aerobic exercise training has yet to be examined in Pre and...

Abstract Angiotensin II (AngII), via the AngII type 1 receptor (AT(1)R), contributes to oxidative stress. Aerobic exercise training (AEXT) reduces the risk of cardiovascular (CV) disease, presumably by reducing the grade of oxidative stress. We investigated the independent and combined influence of the AGTR1 A1166C and -825 T/A polymorphisms on oxi...

This update of the human gene map for physical performance and health-related fitness phenotypes covers the research advances reported in 2006 and 2007. The genes and markers with evidence of association or linkage with a performance or a fitness phenotype in sedentary or active people, in responses to acute exercise, or for training-induced adapta...

Abnormal cholesterol metabolism, including low intestinal cholesterol absorption and elevated synthesis, is prevalent in diabetes, obesity, hyperlipidemia, and the metabolic syndrome. Diet-induced weight loss improves cholesterol absorption in these populations, but it is not known if endurance exercise training also improves cholesterol homeostasi...

Abnormal cholesterol metabolism, including low intestinal cholesterol absorption and elevated synthesis, is prevalent in diabetes, obesity, hyperlipidemia, and the metabolic syndrome. Diet-induced weight loss improves cholesterol absorption in these populations, but it is not known if endurance exercise training also improves cholesterol homeostasi...

The objective of the study was to determine whether ethnicity interacts with the APOE genotype to influence conventionally measured high-density lipoprotein cholesterol (HDL-C) subfraction levels and nuclear magnetic resonance-measured (HDL(NMR)-C) particle size at baseline and after training, and the changes with training. After a 6-week dietary s...

We investigated the association between soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) levels and obesity in older women. Fifty-one postmenopausal women (10 lean, 22 overweight, and 19 obese) were included in this small retrospective analysis. Plasma sLOX-1 levels were measured using a chemiluminescent enzyme-linked immuno...

The lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) expressed on vascular cells plays a major role in atherogenesis by internalizing and degrading oxidized low-density lipoprotein. LOX-1 can be cleaved from the cell surface and released as soluble LOX-1 (sLOX-1), and elevated sLOX-1 levels may be indicative of atherosclerotic plaque...

Perilipin proteins are known to regulate intracellular lipolysis in adipocytes. A haplotype of two perlipin gene ( PLIN ) single nucleotide polymorphisms (SNPs), 13041A>G and 14995A>T, has been previously associated with obesity risk. We hypothesized that this haplotype associates with body fatness phenotypes before and after a 6‐mo aerobic exercis...

Our objective was to investigate the relationship between the E23K genetic variant in the KCNJ11 gene, which encodes for the Kir6.2 subunit of the inward rectifier K+ channel family, and glucose and insulin metabolism and cardiovascular (CV) function in the sedentary state and their responses to exercise training. Two hundred and fourteen healthy s...

To examine the influence of insulin-like growth factor (IGF) pathway gene polymorphisms on muscle mass and strength responses to strength training (ST), we studied 128 White and Black men and women before and after a 10-wk single-leg knee extension ST program. One-repetition maximum strength, muscle volume (MV) via computed tomography, and muscle q...

In endothelial cells, NF-kappaB is an important intracellular signaling molecule by which changes in wall shear stress are transduced into the nucleus to initiate downstream endothelial nitric oxide synthase (NOS3) gene expression. We investigated whether NF-kappa light-chain gene enhancer in B cells 1 (NFKB1) promoter polymorphism ((-94)NFKB1 I/D,...

In the endothelial cells, the nuclear factor–kappa B is an important intracellular signaling molecule by which changes in wall shear stress are transduced into the nucleus to initiate downstream endothelial nitric oxide synthase (NOS3) gene expression. We investigated whether the NFKB1 promoter polymorphism (-94 NFKB1 I/D) was associated with (1) N...

The coagulation cascade plays a critical role in the development of cardiovascular disease (CVD). Elevated plasma prothrombin fragment 1 + 2 (F1 + 2) and factor VIII antigen (FVIII:Ag) levels have been associated with a hypercoagulable state, enhancing the risk for vascular thrombotic events. Aerobic training is known to reduce CVD risk, and an imp...

Endurance exercise training improves plasma lipoprotein and lipid profiles and reduces cardiovascular disease risk. However, the effect of endurance exercise training, independent of diet and body fat phenotypes, on plasma lipoprotein subfraction particle concentration, size, and composition as measured by nuclear magnetic resonance (NMR) spectrosc...

changes in vascular morphology and function with increasing age clearly are significant contributors to age-related increases in cardiovascular disease (CVD). In addition, the presence of CVD risk factors, such as hypertension, hyperlipidemia, diabetes, and smoking, have been shown to cause