Endurance exercise training volume is not associated with progression of coronary artery calcification

Background Recent cross‐sectional studies have suggested a dose‐dependent relationship between lifelong exposure to physical activity and the burden of calcified coronary artery disease (CAD). No longitudinal studies have addressed this concern. Hypothesis Exercise volume is associated with progression of coronary artery calcium (CAC), defined as ≥10 units increase in CAC score. Methods Sixty‐one recreational athletes who were assessed by coronary computed tomography angiography (CCTA) as part of the NEEDED 2013/14 study were re‐assessed 4‐5 years later, in 2018. Results Subjects were 45.9 ± 9.6 years old at inclusion, and 46 (74%) were male. Between 2013 and 2018, the participants reported median 5 (range: 0‐20, 25th‐75th percentile: 4‐6) hours of high‐intensity exercise per week. None of the included subjects smoked during follow‐up. At inclusion, 21 (33%) participants had coronary artery calcifications. On follow‐up CCTA in 2018, 15 (25%) subjects had progressive coronary calcification (≥10 Agatston units increase in CAC). These subjects were older (53 ± 9 vs 44 ± 9 years old, P = .002) and had higher levels of low‐density lipoprotein at baseline (3.5 (2.9‐4.3) vs 2.9 (2.3‐3.5) mmol/L, P = .031) as compared to subjects with stable condition. No relationship was found between hours of endurance training per week and progression of coronary artery calcification. In multiple regression analysis, age and baseline CAC were the only significant predictors of progressive CAC. Conclusion No relationship between exercise training volume and the progression of coronary artery calcification was found in this longitudinal study of middle‐aged recreational athletes.publishedVersio

The Genomic Analysis of Erythrocyte microRNA Expression in Sickle Cell Diseases

BACKGROUND: Since mature erythrocytes are terminally differentiated cells without nuclei and organelles, it is commonly thought that they do not contain nucleic acids. In this study, we have re-examined this issue by analyzing the transcriptome of a purified population of human mature erythrocytes from individuals with normal hemoglobin (HbAA) and homozygous sickle cell disease (HbSS). METHODS AND FINDINGS: Using a combination of microarray analysis, real-time RT-PCR and Northern blots, we found that mature erythrocytes, while lacking ribosomal and large-sized RNAs, contain abundant and diverse microRNAs. MicroRNA expression of erythrocytes was different from that of reticulocytes and leukocytes, and contributed the majority of the microRNA expression in whole blood. When we used microRNA microarrays to analyze erythrocytes from HbAA and HbSS individuals, we noted a dramatic difference in their microRNA expression pattern. We found that miR-320 played an important role for the down-regulation of its target gene, CD71 during reticulocyte terminal differentiation. Further investigation revealed that poor expression of miR-320 in HbSS cells was associated with their defective downregulation CD71 during terminal differentiation. CONCLUSIONS: In summary, we have discovered significant microRNA expression in human mature erythrocytes, which is dramatically altered in HbSS erythrocytes and their defect in terminal differentiation. Thus, the global analysis of microRNA expression in circulating erythrocytes can provide mechanistic insights into the disease phenotypes of erythrocyte diseases

MicroRNA-96 Directly Inhibits γ-Globin Expression in Human Erythropoiesis

Fetal hemoglobin, HbF (α2γ2), is the main hemoglobin synthesized up to birth, but it subsequently declines and adult hemoglobin, HbA (α2β2), becomes predominant. Several studies have indicated that expression of the HbF subunit γ-globin might be regulated post-transcriptionally. This could be confered by ∼22-nucleotide long microRNAs that associate with argonaute proteins to specifically target γ-globin mRNAs and inhibit protein expression. Indeed, applying immunopurifications, we found that γ-globin mRNA was associated with argonaute 2 isolated from reticulocytes that contain low levels of HbF (<1%), whereas association was significantly lower in reticulocytes with high levels of HbF (90%). Comparing microRNA expression in reticulocytes from cord blood and adult blood, we identified several miRNAs that were preferentially expressed in adults, among them miRNA-96. The overexpression of microRNA-96 in human ex vivo erythropoiesis decreased γ-globin expression by 50%, whereas the knock-down of endogenous microRNA-96 increased γ-globin expression by 20%. Moreover, luciferase reporter assays showed that microRNA-96 negatively regulates expression of γ-globin in HEK293 cells, which depends on a seedless but highly complementary target site located within the coding sequence of γ-globin. Based on these results we conclude that microRNA-96 directly suppresses γ-globin expression and thus contributes to HbF regulation

P4425The exercise-induced troponin I elevation is highly correlated with power output during exercise in recreational cyclists with coronary atherosclerosis

Abstract Background Following strenuous exercise there is an increase cardiac Troponins (cTn) elevation considered being a physiological response. During prolonged strenuous physical activity, high work-loads may induce demand myocardial ischemia due to an oxygen demand/supply mismatch in susceptible subjects, causing an excessive cTn elevation. Purpose This study aimed to assess the relationship between exercise-induced cTnI elevation and direct measurement of work performed during prolonged strenuous exercise in subjects with and without atherosclerotic CAD. Methods Work during a 91 km mountain bike race was quantified by Stages™ power meters. Power (Watt) and heart rate data were stored in Garmin™ Forerunner 935 monitors. Coronary computed tomography angiography was performed after the race. Blood pressure was measured 4 times during the race. Blood samples (hs-cTnI from Abbot Diagnostics) were obtained one day prior to the race and at 3 and 24 h after the race. Data are presented as mean±SD or median (25th and 75th percentile). Results 40 subjects (10 women) were included in the final analysis. 15 Participants (4 women) had atherosclerosis, none had obstructive CAD. These participants were significantly older (55±8 years vs. 46±8 years p=0.007) and had higher training volumes (METS: 69 (64–102) hrs/week) compared with normal subjects (METS: 51 (33–88) hrs/week) (p=0.03). Baseline cTnI was higher (p=0.04) in the atherosclerotic group (4.5 (3.4–8.8) ng/L) compared with normals (2.6 (1.6–4.8) ng/L). There were no differences in baseline blood pressure, peak VO2 max, heart rate or BMI. There was no significant difference in race duration between normals (3.9 (3.5–4.5) hrs) and subjects with atherosclerosis (4.1 (3.6–4.5) hrs). During the race there were no differences in peak power or peak Watt/kg. cTnI increased after the race in all participants, but there were no differences between groups: 3h: atherosclerosis: 89 (27–131) ng/L vs. normal 77 (36–104) ng/L, 24h: atherosclerosis: 13 (6.3–23.7) ng/L vs. normal: 17 (12–37) ng/L. There were no significant difference between the groups in average power during the race: atherosclerosis: 167±50 Watt vs. 174 (±50) Watt or ratio: 2.0±0.49 Watt/kg vs 2.2±0.58 Watt/kg during the race. Maximal systolic and diastolic blood pressures during the race were higher (p=0.002) in the atherosclerotic group: SBP: 241±14 mmHg vs. 219±26 mmHg, DBP: 107±8 vs 95±8 mmHg. In atherosclerotic subjects cTnI both at 3h and 24 h were highly correlated (p&lt;0.001) with Watt/kg ratio during the race in contrast to no correlations in the normal group (Figure). Conclusions Our findings suggest that the presence of coronary atherosclerosis, even in the absences of significant stenosis, alters the relationship between workload and the troponin response. This indicates different release kinetics in exercise-induced cTn in participants with and without CAD, with prolonged elevation in cTnI in CAD subjects exceeding the highest work-intensities. Acknowledgement/Funding Grant Western Norway Health service, Grant ConocoPhillips, Grant Simon Fougner Hartmanns Familyfund </jats:sec

Is there an exercise duration threshold for exercise-induced troponin elevation in healthy recreational athletes? The NEEDED 2014 advanced heart rate monitor substudy

Abstract Background/Introduction Following prolonged strenuous exercise there is an exercise-induced troponin (cTn) elevation in healthy individuals. The precise mechanisms and clinical consequence of this cTn elevation remain to be determined. It has recently been demonstrated that exercise intensity, exceeding a heart rate (HR) of 150 bpm, is correlated with exercise-induced cTn elevation. Purpose The present work aims to determine if there is a threshold for exercise duration with a HR exceeding 150 bpm associated with an excessive exercise-induced cTn elevation. Methods A total of 177 healthy subjects were included in the present analysis of HR data obtained from sport watches used during a 91-km recreational mountain bike cycle race. Clinical status, cTnI, ECGs, blood pressure and demographics were obtained 24 h prior to- and at 3 h and 24 h after the race. Results are reported as median and 25th and 75th percentile. We used Tree regression to determine the association between elevated cTnI and exercise duration exceeding a HR of 150 bpm. Results Subjects were 82% (n=146) males, 44 (39–51) years, with a race time of 3.5 (3.1–3.9) h. Baseline cTnI was 1.9 (1.6–3.3) ng/L. There was a cTnI elevation in all study participants at 3 h, cTnI: 60.0 (36.0–99.3) ng/L, with a significant (p&amp;lt;0.001) reduction at 24 hours following exercise, cTnI: 10.9 (6.1–22.4) ng/L. Tree regression identified 168 min of exercise, with a HR exceeding 150 bpm, to be associated with an excessive increase in cTnI both at 3 h, and at 24 h following the race (figure). The median cTn values above and below the threshold are presented in the Table. Conclusion The present analysis suggests that exceeding a specific duration of high intensity exercise may be associated with excessive cTn elevation in susceptible individuals. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Western Norway Health authoritites. </jats:sec