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Scientific Programme

Sports and Exercise Medicine and Health

OP-MH23 - Exercise and vascular function

Date: 02.07.2024, Time: 13:30 - 14:45, Lecture room: Dochart 1

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Chair TBA

Chair

TBA
TBA
TBA

ECSS Paris 2023: OP-MH23

Speaker A Xuyun Liu

Speaker A

Xuyun Liu
Xi’an Jiaotong University, School of Life Science and Technology and Frontier Institute of Science and Tech
China
"The mechanical mechanism of exercise improving hyperlipidemia-induced endothelial injury: Shear stress activates PIEZO1 to promote mitochondrial fusion"

INTRODUCTION: Physical exercise improves hyperlipidemia-induced endothelial injury by reducing circulatory lipid levels and enhancing mitochondrial function in vascular endothelial cells. However, the exact mechanism underlying its protective effects remains uncertain, despite recent research indicating that blood flow shear stress is a key mechanism through which exercise enhances endothelial function. It is still unclear whether blood flow shear stress contributes to the exercise-induced improvement of endothelial injury caused by hyperlipidemia, and the specific mitochondrial molecular mechanism remains to be elucidated. Piezo1, as a newly discovered mechanosensitive ion channel protein, plays a crucial role in response to mechanical stress. METHODS: In this study, we utilized long-term and short-term hyperlipidemia models to elucidate the role of exercise in improving vascular damage caused by hyperlipidemia and whether fluid shear stress is involved. Furthermore, pharmacological interventions (PIEZO1 agonists and inhibitors) and PIEZO1 knockout mice were employed to validate PIEZO1 as a key molecule in exercise-induced improvement of hyperlipidemia-associated vascular damage. Finally, utilizing cellular and molecular biology techniques, we elucidated the molecular mechanism by which fluid shear stress promotes mitochondrial fusion through PIEZO1, thereby improving endothelial function. RESULTS: This study demonstrated that exercise can increase blood flow shear stress and ameliorate endothelial injury in both long-term and acute hyperlipidemia models. Additionally, intravenous injection of the Piezo1 agonist Yoda1 into the tail vein has a similar effect to exercise in mitigating endothelial injury. Conversely, the beneficial effects of exercise in improving endothelial injury diminish in endothelial-specific Piezo1 knockout mice and following intravenous injection of the Piezo1 inhibitor GsTMx-4, indicating that Piezo1 is a crucial molecule for exercise-induced improvement of endothelial injury. Furthermore, in vitro experiments revealed that isolated mitochondria can directly respond to fluid shear stress and Yoda1. Blood flow shear stress can enhance endothelial cell mitochondrial fusion and function by activating the Piezo1-Mfn2-eNOS signaling axis. CONCLUSION: These findings unveil a novel mechanism by which exercise promotes endothelial cell function by increasing blood flow shear stress to activate the Piezo1-Mfn2-eNOS signaling axis, and suggest that Piezo1 may present a new target for preventing and treating hyperlipidemia-induced endothelial injury.

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ECSS Paris 2023: OP-MH23

Speaker B Letizia Giusti

Speaker B

Letizia Giusti
Università di Pavia, Medicine
Italy
"Microvascular function impairments after steps reduction in young subjects"

INTRODUCTION: Inactivity is an important and independent risk factor for all-cause mortality, and there is increasing evidence of the importance of minimizing sedentary behavior to reduce the risk of cardiovascular diseases (1). Endothelial dysfunction plays an important role in the pathogeneses of cardiovascular diseases, and impaired endothelium dependent dilation is directly linked with cardiovascular morbidity and mortality (2). Bedrest, which is a classical model utilized to study the physiological effects of severe inactivity, showed a negative impact on endothelial function (3,4). The effects of steps reduction, a milder form of inactivity, on microvascular responsiveness are currently unclear. In the present study, we investigate the effects of 14 days of steps reduction on microvascular function, evaluating acute post-occlusive reactive hyperemia by near-infrared spectroscopy (NIRS). METHODS: Eighteen young subjects (12 males and 6 females; age: 22±3y, weight: 69.1±11.9kg, height: 172±7cm) were assessed before (PRE) and after 14 days of steps reduction (SR). Their physical activity was monitored through an accelerometer worn on the waist. Microvascular function was estimated by monitoring changes of tissue saturation index (TSI) during a prolonged ischemia followed by a reperfusion phase. The rate of muscle deoxygenation during the first minute of occlusion (Slope1) was used as proxy of resting muscle oxygen uptake. Time of ischemia (t-isch) and the lowest TSI value reached during occlusion (TSImin) were calculated to estimate the ischemic vasodilatory stimulus. The rate of muscle reperfusion during 10s (Slope2-10s) post-ischemia and the magnitude of reperfusion (TSIpeak) were calculated. RESULTS: Steps count was effectively reduced by 82% from PRE to SR. Slope1 was not different between PRE (-0.11±0.07%*s-1) and SR (-0.12±0.10%*s-1; p=0.436). TSImin was lower after SR compared to PRE (46.2±7.1% vs 43.2±8.5%, respectively; p<0.05). Slope2-10s was similar between PRE (1.16±0.59%*s-1) and SR (1.12±0.38%*s-1; p=0.573) but it resulted significantly reduced after SR (-13%) when normalized for the ischemic vasodilatory stimulus. CONCLUSION: After 14 days of steps reduction, resting muscle oxygen uptake did not change whereas endothelial function was impaired. Thus, a mild reduction of daily activity induced alterations at microvascular level, which are probably due to lower nitric oxide (NO) bioavailability and partial structural vascular modifications.

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ECSS Paris 2023: OP-MH23

Speaker C María Rúa Alonso

Speaker C

María Rúa Alonso
University of A Coruña, Department of Physical and Sports Education, Performance and health group
Spain
"Can set configuration modulate the arterial stiffness and post-exercise hypotension response in postmenopausal women?"

INTRODUCTION: Menopause is a critical phase in women’s health, increasing the risks of hypertension and vascular dysfunction (1). Resistance exercise (RE) can promote a post-exercise hypotensive response in postmenopausal women (2). Set configuration can modulate the acute cardiovascular response to RE (3,4). However, menopause may influence the acute effects to exercise (2). Therefore, the aim of this study was to explore arterial stiffness and blood pressure response in postmenopausal women after RE protocols with different set configurations. METHODS: 50 postmenopausal women with a physically active lifestyle (37 normotensive/13 hypertensive) participated in this study funded by the Spanish Ministry of Science and Innovation (PID2021-124277OB). After a medical screening and familiarisation with the RE protocol composed by four exercises, each woman completed one control (CON) and three experimental sessions equated by intensity (12RM load), volume (144 reps) and total resting time (18min), but differing in set configuration: 9 sets of 4 reps with 45s rest (9S); 6 sets of 6 reps with 72s rest (6S); and 4 sets of 9 reps with 120s rest (4S). Arterial stiffness, measured by pulse wave velocity (PWV), was assessed before, immediately after, and 60 min after session. Blood pressure, including systolic (sBP), diastolic (dBP), and mean arterial pressure (MAP), as well as low frequency of SBP oscillations (LFsBP), were evaluated before and after each session at intervals of 5-15, 15-25, 30-40, and 40-50min. RESULTS: No differences between normo- and hypertensive participants were observed. ANOVA analysis detected a main effect of time, session, and time×session interaction (p≤0.002) for PWV. Immediately after session, all RE protocols caused higher values than CON (p≤0.006). Increases compared to baseline were observed only after 6S and 9S (p≤0.039), with no significant differences between the experimental sessions. After 60min from the end of the session, all RE protocols showed a reduction in PWV compared to immediately post-exercise records (p≤0.005), without differences between experimental sessions and CON (p≥0.075). Only a main effect of time was observed for sBP, MAP and LFsBP (p≤0.021). CONCLUSION: Set configuration may modulate the arterial stiffness response after exercise, despite the absence of a post-exercise hypotension response in physically active postmenopausal women. Long set configurations increase arterial stiffness without providing the hypotensive benefit. Thus, in order to reduce the cardiovascular risk while still reaping the benefits of RE, short set configurations (i.e., an intensity of effort of 33%, 4 out of 12) should be recommended for postmenopausal women, similar to healthy young people (3,4). REFERENCES 1) Hulteen et al., Int. J. Sports Med, 2023 2) Le Bourvellec et al., J Appl Physiol, 2024 3) Mayo et al., J Strength Cond Res, 2016 4) Rúa-Alonso et al., Eur J Appl Physiol, 2020

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ECSS Paris 2023: OP-MH23