Exercise-Induced Circulating Hematopoietic Stem and Progenitor Cells in Well-Trained Subjects

It has been proposed that exercise-induced systemic oxidative stress increases circulating hematopoietic stem and progenitor cell (HPC) number in active participants, while HPC clonogenicity is reduced post-exercise. However, HPCs could be protected against exercise-induced reactive oxygen species in a trained state. Therefore, we characterized the acute exercise-induced HPC profile of well-trained participants including cell number, clonogenicity, and clearance. Twenty-one healthy, well-trained participants—12 runners, 9 cyclists; age 30.0 (4.3) years—performed a strenuous acute exercise session consisting of 4 bouts of 4-min high-intensity with 3-min low-intensity in-between, which is known to elicit oxidative stress. Average power/speed of intense phases was 85% of the peak achieved in a previous incremental test. Before and 10 min after exercise, CD34+/45dim cell number and clonogenicity, total oxidative (TOC), and antioxidative (TAC) capacities, as well as CD31 expression on detected HPCs were investigated. TOC significantly decreased from 0.093 (0.059) nmol/l to 0.083 (0.052) nmol/l post-exercise (p = 0.044). Although HPC proportions significantly declined below baseline (from 0.103 (0.037)% to 0.079 (0.028)% of mononuclear cells, p < 0.001), HPC concentrations increased post-exercise [2.10 (0.75) cells/μl to 2.46 (0.98) cells/μl, p = 0.002] without interaction between exercise modalities, while HPC clonogenicity was unaffected. Relating HPC concentrations and clonogenicity to exercise session specific (anti-) oxidative parameters, no association was found. CD31 median fluorescent intensity expression on detected HPCs was diminished post-exercise [from 1,675.9 (661.0) to 1,527.1 (558.9), p = 0.023] and positively correlated with TOC (rrm = 0.60, p = 0.005). These results suggest that acute exercise-reduced oxidative stress influences HPC clearance but not mobilization in well-trained participants. Furthermore, a well-trained state protected HPCs’ clonogenicity from post-exercise decline.ISSN:1664-042

Acute exercise-induced glycocalyx shedding does not differ between exercise modalities, but is associated with total antioxidative capacity

Objectives Regular physical exercise is known to protect endothelial integrity. It has been proposed that acute exercise-induced changes of the (anti-)oxidative system influence early (glycocalyx shedding) and sustained endothelial activation (shedding of endothelial cells, ECs) as well as endothelial-cell repair by circulating hematopoietic stem and progenitor cells (HPCs). However, results are not conclusive and data in trained participants performing different exercise modalities is lacking. Design Eighteen healthy, well-trained participants (9 runners, 9 cyclists; age: 29.7 ± 4.2 yrs) performed a strenuous acute exercise session consisting of 4 bouts of 4-min high-intensity with decreasing power profile and 3-min low-intensity in-between. Methods Average power/speed of intense phases was 85% of the peak achieved in a previous incremental test. Before and shortly after exercise, total oxidative and antioxidative capacities (TAC), shedding of syndecan-1, heparan sulfate, hyaluronan, ECs, and circulating HPCs were investigated. Results TAC decreased from 1.81 ± 0.42 nmol/L to 1.47 ± 0.23 nmol/L post-exercise (p = 0.010) only in runners. Exercise-induced early and sustained endothelial activation were enhanced post-exercise- syndecan-1: 103.2 ± 63.3 ng/mL to 111.3 ± 71.3 ng/mL, heparan sulfate: from 2637.9 ± 800.1 ng/mL to 3197.1 ± 1416.3 ng/mL, both p < 0.05; hyaluronan: 84.3 ± 21.8 ng/mL to 121.4 ± 29.4 ng/mL, ECs: from 6.6 ± 4.5 cells/μL to 9.5 ± 6.2 cells/μL, both p < 0.01; results were not different between exercise modalities and negatively related to TAC concentrations post-exercise. HPC proportions and self-renewal ability were negatively, while EC concentrations were positively associated with circulating hyaluronan concentrations. Conclusions These results highlight the importance of the antioxidative system to prevent the endothelium from acute exercise-induced vascular injury – independent of exercise modality – in well-trained participants. Endothelial-cell repair is associated with hyluronan signaling, possibly a similar mechanism as in wound repair.ISSN:1440-244

Acute Exercise in Hypobaric Hypoxia Attenuates Endothelial Shedding in Subjects Unacclimatized to High Altitudes

Travel of unacclimatized subjects to a high altitude has been growing in popularity. Changes in endothelial shedding [circulating endothelial cells (ECs)] and hematopoietic stem and progenitor cells (CPCs) during physical exercise in hypobaric hypoxia, however, are not well understood. We investigated the change in ECs and CPCs when exposed to high altitude, after acute exercise therein, and after an overnight stay in hypobaric hypoxia in 11 healthy unacclimatized subjects. Blood withdrawal was done at baseline (520 m a.s.l.; baseline), after passive ascent to 3,883 m a.s.l. (arrival), after acute physical exercise (±400 m, postexercise) and after an overnight stay at 3,883 m a.s.l. (24 h). Mature blood cells, ECs, and CPCs were assessed by a hematology analyzer and flow cytometry, respectively. The presence of matrix metalloproteinases (MMPs), their activity, and hematopoietic cytokines were assessed in serum and plasma. EC and CPC concentrations significantly decreased after exercise (p = 0.019, p = 0.007, respectively). CPCs remained low until the next morning (24 h, p = 0.002), while EC concentrations returned back to baseline. MMP-9 decreased at arrival (p = 0.021), stayed low postexercise (p = 0.033), and returned to baseline at 24 h (p = 0.035 to postexercise). MMP-activity did not change throughout the study. Circulating MMP-9 concentrations, but not MMP-activity, were associated with EC concentrations (rrm = 0.48, p = 0.010). CPC concentrations were not linked to hematopoietic cytokines. Acute exercise at high altitude attenuated endothelial shedding, but did not enhance regenerative CPCs. Results were not linked to endothelial matrix remodeling or CPC mobilization. These results provide information to better understand the endothelium and immature immune system during an active, short-term sojourn at high altitude.ISSN:1664-042

Correlation analysis of free norepinephrine (free NE) to circulating hematopoietic stem and progenitor cell count (CPC,[6]) under normoxic and hypoxic conditions (NE sampled pre, directly after; CPCs sampled pre, 10 min post; n = 20); Sampling points were the rest and peak points of the two parameters.

<p>The increase in CPCs is strongly correlated with a preceding increase in free NE.</p

Free/bound epinephrine levels (pg/ml).

<p>Significant differences to baseline (repeated-measures ANOVA with Bonferroni posthoc comparisons) are indicated as follows: *p<0.05.</p><p>Free/bound epinephrine levels (pg/ml).</p

Free/bound norepinephrine levels (pg/ml).

<p>Significant differences to baseline (repeated-measures ANOVA with Bonferroni posthoc comparisons) are indicated as follows: ***p<0.001, **p<0.01, *p<0.05.</p><p>Free/bound norepinephrine levels (pg/ml).</p