Background—Cardiac remodeling occurs in response to regular athletic training, and the degree of remodeling is associated with fitness. Understanding the myocardial structural changes in athlete’s heart is important to develop tools that differentiate athletic from cardiomyopathic change. We hypothesized that athletic left ventricular hypertrophy is a consequence of increased myocardial cellular rather than extracellular mass as measured by cardiovascular magnetic resonance.Methods and Results—Forty-five males (30 athletes and 15 sedentary age-matched healthy controls) underwent comprehensive cardiovascular magnetic resonance studies, including native and postcontrast T1 mapping for extracellular volume calculation. In addition, the 30 athletes performed a maximal exercise test to assess aerobic capacity and anaerobic threshold. Participants were grouped by athleticism: untrained, low performance, and high performance (O2max <60 or>60 mL/kg per min, respectively). In athletes, indexed cellular mass was greater in high- than low-performance athletes 60.7±7.5 versus 48.6±6.3 g/m2; P<0.001), whereas extracellular mass was constant (16.3±2.2 versus 15.3±2.2 g/m2; P=0.20). Indexed left ventricular end-diastolic volume and mass correlated with O2max (r=0.45, P=0.01; r=0.55, P=0.002) and differed significantly by group (P=0.01; P<0.001, respectively). Extracellular volume had an inverse correlation with O2max (r=−0.53, P=0.003 and left ventricular mass index (r=-0.44, P=0.02).Conclusions—Increasing left ventricular mass in athlete’s heart occurs because of an expansion of the cellular compartment while the extracellular volume becomes relatively smaller: a difference which becomes more marked as left ventricular mass increases. Athletic remodeling, both on a macroscopic and cellular level, is associated with the degree of an individual’s fitness. Cardiovascular magnetic resonance ECV quantification may have a future role in differentiating athlete’s heart from change secondary to cardiomyopathy.

Background Epidemiological studies have indicated an inverse association between citrus fruit consumption and cardiovascular disease (CVD) risk. There is, however, a paucity of data concerning effects of blood orange juice (BOJ) intake on endothelial function and cardiovascular risk biomarkers. Objectives We examined short-term effects of BOJ on endothelial function, blood pressure, lipid profile, and inflammatory markers in healthy participants of European origin who were overweight or obese. Methods In a randomized, controlled, single-blind, crossover trial, 15 men and women (age: 28.7 ± 6.5 y; BMI: 28.3 ± 3.1 kg/m2) consumed BOJ or a sugar-matched control drink (CD) (200 mL twice daily) for 2 wk with a washout period of 1 wk. Endothelial function, measured as flow-mediated dilation (FMD) (primary outcome), and the secondary outcomes blood pressure, anthropometric measures, lipid profile, inflammatory markers, markers of vasodilation and vasoconstriction, and urinary flavanone metabolites were evaluated prior to and at the end of each treatment period following an overnight fast. Changes between treatments over time were assessed using repeated-measures ANOVA. Results The results demonstrate a significant increase in FMD following BOJ consumption (pre: 8.15% ± 2.92%; post: 10.2% ± 3.31%; P = 0.002) compared with CD (pre: 8.11% ± 2.52%; post: 7.77% ± 2.43%; time × treatment interaction: P = 0.001). Concurrent significant increases in urinary hesperetin-3′-glucuronide and hesperetin-7-glucuronide were observed following BOJ supplementation only (time × treatment interaction: P ≤ 0.01). Baseline blood pressure, lipid profile, high-sensitivity C-reactive protein, and endothelin-1 were generally within healthy ranges and unaffected by the intervention. Conclusions A 2-wk consumption of BOJ exerted favorable effects on endothelial function in healthy women and men who were overweight or obese, which is likely mediated by the combined actions of anthocyanin and flavanone metabolites on mechanisms that contribute to enhancing NO bioavailability. This trial was registered at clinicaltrials.gov as NCT03611114.

Background About half of heart failure (HF) patients, while having preserved left ventricular function, suffer from diastolic dysfunction (so-called HFpEF). No specific therapeutics are available for HFpEF in contrast to HF where reduced ejection fractions (HFrEF) can be treated pharmacologically. Myocardial titin filament stiffening, endothelial dysfunction, and skeletal muscle (SKM) myopathy are suspected to contribute to HFpEF genesis. We previously described small molecules interfering with MuRF1 target recognition thereby attenuating SKM myopathy and dysfunction in HFrEF animal models. The aim of the present study was to test the efficacy of one small molecule (MyoMed-205) in HFpEF and to describe molecular changes elicited by MyoMed-205. Methods Twenty-week-old female obese ZSF1 rats received the MuRF1 inhibitor MyoMed-205 for 12 weeks; a comparison was made to age-matched untreated ZSF1-lean (healthy) and obese rats as controls. LV (left ventricle) function was assessed by echocardiography and by invasive haemodynamic measurements until week 32. At week 32, SKM and endothelial functions were measured and tissues collected for molecular analyses. Proteome-wide analysis followed by WBs and RT-PCR was applied to identify specific genes and affected molecular pathways. MuRF1 knockout mice (MuRF1-KO) SKM tissues were included to validate MuRF1-specificity. Results By week 32, untreated obese rats had normal LV ejection fraction but augmented E/e′ ratios and increased end diastolic pressure and myocardial fibrosis, all typical features of HFpEF. Furthermore, SKM myopathy (both atrophy and force loss) and endothelial dysfunction were detected. In contrast, MyoMed-205 treated rats had markedly improved diastolic function, less myocardial fibrosis, reduced SKM myopathy, and increased SKM function. SKM extracts from MyoMed-205 treated rats had reduced MuRF1 content and lowered total muscle protein ubiquitination. In addition, proteomic profiling identified eight proteins to respond specifically to MyoMed-205 treatment. Five out of these eight proteins are involved in mitochondrial metabolism, dynamics, or autophagy. Consistent with the mitochondria being a MyoMed-205 target, the synthesis of mitochondrial respiratory chain complexes I + II was increased in treated rats. MuRF1-KO SKM controls also had elevated mitochondrial complex I and II activities, also suggesting mitochondrial activity regulation by MuRF1. Conclusions MyoMed-205 improved myocardial diastolic function and prevented SKM atrophy/function in the ZSF1 animal model of HFpEF. Mechanistically, SKM benefited from an attenuated ubiquitin proteasome system and augmented synthesis/activity of proteins of the mitochondrial respiratory chain while the myocardium seemed to benefit from reduced titin modifications and fibrosis.

BackgroundAthletic training leads to remodelling of both left and right ventricles with increased myocardial mass and cavity dilatation. Whether changes in cardiac strain parameters occur in response to training is less well established. In this study we investigated the relationship in trained athletes between cardiovascular magnetic resonance (CMR) derived strain parameters of cardiac function and fitness.MethodsThirty five endurance athletes and 35 age and sex matched controls underwent CMR at 3.0 T including cine imaging in multiple planes and tissue tagging by spatial modulation of magnetization (SPAMM). CMR data were analysed quantitatively reporting circumferential strain and torsion from tagged images and left and right ventricular longitudinal strain from feature tracking of cine images. Athletes performed a maximal ramp-incremental exercise test to determine the lactate threshold (LT) and maximal oxygen uptake (V̇O2max).ResultsLV circumferential strain at all levels, LV twist and torsion, LV late diastolic longitudinal strain rate, RV peak longitudinal strain and RV early and late diastolic longitudinal strain rate were all lower in athletes than controls. On multivariable linear regression only LV torsion (beta = −0.37, P = 0.03) had a significant association with LT. Only RV longitudinal late diastolic strain rate (beta = −0.35, P = 0.03) had a significant association with V̇O2max.ConclusionsThis cohort of endurance athletes had lower LV circumferential strain, LV torsion and biventricular diastolic strain rates than controls. Increased LT, which is a major determinant of performance in endurance athletes, was associated with decreased LV torsion. Further work is needed to understand the mechanisms by which this occurs.

Endothelial cell phenotype and endothelial function are regulated by hemodynamic forces, particularly wall shear stress (WSS). During a single bout of exercise, the specific exercise protocol can affect in-exercise WSS patterns and, consequently, endothelial function. MicroRNAs might provide a biomarker of in-exercise WSS pattern to indicate whether a specific exercise bout will have a positive effect on endothelial function. We evaluated the effect of acute interval (IT) and continuous (CON) in-exercise WSS patterns upon postexercise endothelial function and circulating microRNA (miR)-21 expression. Methods and results: 13 participants performed CON and 3 different IT exercise protocols matched for duration and intensity on separate days. Oxygen uptake, heart rate, and brachial artery blood flow were recorded throughout the exercise. Brachial artery flow-mediated dilation (FMD) was performed pre-exercise and 15 min postexercise. Plasma samples were acquired pre-exercise and 6 h postexercise to determine miR-21 expression. In-exercise shear rate (SR) patterns (a surrogate of WSS) differed according to the CON or IT work-rate profile. In-exercise anterograde SR was greater in CON than IT exercise ( P < 0.05), but retrograde SR was equivalent between exercise protocols ( P > 0.05). Oscillatory shear index was higher during IT versus CON exercise ( P < 0.05). Postexercise FMD increased (pre: 7.08% ± 2.95%, post: 10.54% ± 4.24%, P < 0.05), whereas miR-21 expression was unchanged (pre: 12.0% ± 20.7% cel-miR-39, post: 11.1 ± 19.3% cel-miR-39, P > 0.05) with no effect of exercise protocol ( P > 0.05). Conclusions: CON and IT exercise induced different SR patterns but equivalent improvements in acute endothelial function. The absence of change in miR-21 expression suggests that miR-21 is not a suitable biomarker of exercise-induced SR. NEW & NOTEWORTHY Interval exercise has the potential to negatively impact vascular adaptations because of repeated oscillations in vascular shear. To our knowledge, we are the first to continuously assess exercise-induced shear throughout different acute exercise protocols and examine its relationship with acute endothelial function and a circulating biomarker of shear (miR-21). These experiments provide clear data indicating enhancement of the acute vascular response from differing interval exercise protocols, with the study also providing detailed vascular and shear responses for future reference.