The effects of moderate and high-intensity exercise on circulating markers of endothelial integrity and activation in young, healthy men

Abstract

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. Young, healthy men ( n = 10) underwent 30-min moderate continuous (MOD) and high-intensity interval (HII) cycling exercise bouts. Venous blood samples were taken immediately before and after exercise for quantification of circulating endothelial cells (CECs), circulating angiogenic cells (CACs), apoptotic and activated endothelial microvesicles (EMVs), thrombomodulin (TM), von Willebrand factor (vWF), syndecan-1, and circulating microRNAs (ci-miRs) 126–3p and 126–5p. Endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery before, 10 min after, and 60 min after exercise. Numbers of CECs and EMVs were unchanged by either exercise bout ( P > 0.05). Numbers of all measured CAC subtypes decreased in response to MOD (21%–34%, P < 0.05), whereas only CD31+/34+/45dim/− CACs decreased following HII (21%, P < 0.05). TM and syndecan-1 increased with both exercise intensities (both ~20%, P < 0.05). HII, but not MOD, increased vWF (88%, P < 0.001), ci-miR-126–3p (92%, P = 0.009) and ci-miR-126–5p (110%, P = 0.01). The changes in several circulating factors correlated with changes in FMD following either one or both intensities. Changes in circulating factors do not support the concept of exercise-induced endothelial cell denudation, apoptosis, or activation, though slight disruption of endothelial glycocalyx and membrane integrity may occur. A related loss of mechanotransduction along with mechanisms underlying endothelial activation and ci-miR-126 secretion may relate to changes in endothelial function. NEW & NOTEWORTHY Using circulating endothelial-derived factors, we show that endothelial denudation, apoptosis, and activation do not appear to increase, whereas disrupted endothelial glycocalyx and membrane integrity may occur during both high-intensity interval and moderate intensity cycling. Increases in factors nonspecific to endothelial damage, including von Willebrand factor and microRNA-126, occurred only after high-intensity interval exercise. These results shed light on the hypothesis that disrupted endothelial integrity contributes to the endothelial function response to exercise.

Changes in circulating microRNA and arterial stiffness following high‐intensity interval and moderate intensity continuous exercise

“…Post‐exercise changes in HR, brachial arterial BP, and aortic BP from baseline are reported in Table 2. We have previously reported mean arterial pressure values (Sapp et al., 2019), however, given the important relationship between arterial BP and stiffness, here we have reported changes to both systolic and diastolic pressures. Heart rate was significantly elevated 10 and 60 min after both the MOD ( p < .0001 and p = .048) and HII bouts ( p < .0001 and p = .0007), and to a greater degree 10 min after HII compared with MOD ( p = .005).…”

“…There were significant changes in aortic BP following HII exercise that did not occur following MOD exercise in our study, and these differences may have contributed to the different responses in central arterial stiffness. We have previously reported no intensity‐dependent differences in either brachial or aortic mean arterial pressures following exercise in these same subjects (Sapp et al., 2019). Furthermore, exercise‐induced changes in arterial stiffness have been reported to occur independently of changes in mean arterial pressure, so it is likely that other mechanisms primarily contributed to the changes in arterial stiffness in our study (Heffernan, Collier, Kelly, Jae, & Fernhall, 2007; Kingwell et al., 1997; Tordi et al., 2010).…”

“…The HII and MOD exercise bouts were well‐matched, eliciting average HRs of 152 ± 7 and 155 ± 10 bpm, respectively ( p = .54) (see reference Sapp et al., 2019). The peak HR was significantly higher during HII compared to MOD (186 ± 8 versus 170 ± 11 bpm, p = .0001).…”

“…Ten young, healthy men were recruited and completed all testing. Detailed demographics are shown in Table 1 (also previously provided (Sapp et al., 2019)).…”

“…Participants were excluded if they had any one of the following: body mass index (BMI) >30 kg/m 2 , brachial systolic blood pressure (BP) >140 mmHg, diastolic BP > 90 mmHg, use of antihypertensive medication, or presence of cardiovascular disease. Information on participants and procedures have been previously reported (Sapp et al., 2019).…”