Shear stress-induced mitochondrial biogenesis decreases the release of microparticles from endothelial cells

Kim, Ji‐Seok; Kim, Boa; Lee, Hojun; Thakkar, Sunny R.; Babbitt, Dianne M.; Eguchi, Satoru; Brown, Michael D.; Park, Joon‐Young

doi:10.1152/ajpheart.00438.2014

Cited by 61 publications

(55 citation statements)

References 50 publications

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“…Here, using strategies allowing the modulation of SIRT1 level in ECFC, we assigned to SIRT1 a critical role in the control of senescence-associated EMP biogenesis. This could be consistent with a recent observation showing that increased EMP levels accompanied a decreased mitochondrial biogenesis through a SIRT1-dependent mechanism 56 . While we do not exclude the involvement of alternative mechanisms impacting on EMP biogenesis, our results establish a new link between the deficiency of SIRT1 and EMP release involving MKK6/p38 MAPK /Hsp27signaling pathway.…”

Section: Discussionsupporting

confidence: 93%

Biogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK6

Simoncini

Château

Robert

et al. 2017

Sci Rep

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Senescent cells may exert detrimental effect on microenvironment through the secretion of soluble factors and the release of extracellular vesicles, such as microparticles, key actors in ageing and cardiovascular diseases. We previously reported that sirtuin-1 (SIRT1) deficiency drives accelerated senescence and dysfunction of endothelial colony-forming cells (ECFC) in PT neonates. Because preterm birth (PT) increases the risk for cardiovascular diseases during neonatal period as well as at adulthood, we hypothesized that SIRT1 deficiency could control the biogenesis of microparticles as part of a senescence–associated secretory phenotype (SASP) of PT-ECFC and investigated the related molecular mechanisms. Compared to control ECFC, PT-ECFC displayed a SASP associated with increased release of endothelial microparticles (EMP), mediating a paracrine induction of senescence in naïve endothelial cells. SIRT1 level inversely correlated with EMP release and drives PT-ECFC vesiculation. Global transcriptomic analysis revealed changes in stress response pathways, specifically the MAPK pathway. We delineate a new epigenetic mechanism by which SIRT1 deficiency regulates MKK6/p38MAPK/Hsp27 pathway to promote EMP biogenesis in senescent ECFC. These findings deepen our understanding of the role of ECFC senescence in the disruption of endothelial homeostasis and provide potential new targets towards the control of cardiovascular risk in individuals born preterm.

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Section: Discussionsupporting

confidence: 93%

Biogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK6

Simoncini

Château

Robert

et al. 2017

Sci Rep

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“…Interestingly, disturbed blood flow increases CD62E + MP concentrations (Jenkins et al., ), suggesting that the repeated increases and decreases in exercise intensity associated with HIIE might be responsible, at least in part, for the lack of change observed in CD62E + MP after interval exercise, provided MP clearance was maintained. Furthermore, laminar shear stress was recently shown to suppress CD62E + MP release (Kim et al., ), supporting our findings of reduced concentrations after MICE and no change after HIIE. Moreover, continuous exercise may be superior to interval exercise in acutely facilitating intercellular communication and/or vascular adaptations as endothelial cells preferentially take up endothelium‐derived MPs rich in microRNAs compared with microRNA‐poor MPs (Alexy et al., ; Diehl et al., ).…”

Section: Discussionsupporting

confidence: 92%

Effect of exercise intensity on circulating microparticles in men and women

Shill

Lansford

Hempel

et al. 2018

Experimental Physiology

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Circulating microparticles (MPs) are biological vectors of information within the cardiovascular system that elicit both deleterious and beneficial effects on the vasculature. Acute exercise has been shown to alter MP concentrations, probably through a shear stress-dependent mechanism, but evidence is limited. Therefore, we investigated the effect of exercise intensity on plasma levels of CD34 and CD62E MPs in young, healthy men and women. Blood samples were collected before, during and after two energy-matched bouts of acute treadmill exercise: interval exercise (10 × 1 min intervals at ∼95% of maximal oxygen uptake V̇O2max) and continuous exercise (65% V̇O2max). Continuous exercise, but not interval exercise, reduced CD62E MP concentrations in men and women by 18% immediately after exercise (from 914.5 ± 589.6 to 754.4 ± 390.5 MPs μl ; P < 0.05), suggesting that mechanisms underlying exercise-induced CD62E MP dynamics are intensity dependent. Furthermore, continuous exercise reduced CD62E MPs in women by 19% (from 1030.6 ± 688.1 to 829.9 ± 435.4 MPs μl ; P < 0.05), but not in men. Although interval exercise did not alter CD62E MPs per se, the concentrations after interval exercise were higher than those observed after continuous exercise (P < 0.05). Conversely, CD34 MPs did not fluctuate in response to short-duration acute continuous or interval exercise in men or women. Our results suggest that exercise-induced MP alterations are intensity dependent and sex specific and impact MP populations differentially.

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“…High physiological laminar shear stress (20 dyn/cm 2 for 24 h) was generated using a previously described modified cone and plate design (3,39). This level of shear stress has been used in several exercise mimetic models (14,26). The cone used in these studies is designed to fit into a 20 ϫ 100-mm tissue culture dish.…”

Section: Methodsmentioning

confidence: 99%

Short-term regular aerobic exercise reduces oxidative stress produced by acute high intraluminal pressure in the adipose microvasculature

Robinson

Fancher

Varadarajan

et al. 2017

American Journal of Physiology-Heart and Circulatory Physiology

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High blood pressure has been shown to elicit impaired dilation in the vasculature. The purpose of this investigation was to elucidate the mechanisms through which high pressure may elicit vascular dysfunction and determine the mechanisms through which regular aerobic exercise protects arteries against high pressure. Male C57BL/6J mice were subjected to 2 wk of voluntary running (~6 km/day) for comparison with sedentary controls. Hindlimb adipose resistance arteries were dissected from mice for measurements of flow-induced dilation (FID; with or without high intraluminal pressure exposure) or protein expression of NADPH oxidase II (NOX II) and superoxide dismutase (SOD). Microvascular endothelial cells were subjected to high physiological laminar shear stress (20 dyn/cm) or static condition and treated with ANG II + pharmacological inhibitors. Cells were analyzed for the detection of ROS or collected for Western blot determination of NOX II and SOD. Resistance arteries from exercised mice demonstrated preserved FID after high pressure exposure, whereas FID was impaired in control mouse arteries. Inhibition of ANG II or NOX II restored impaired FID in control mouse arteries. High pressure increased superoxide levels in control mouse arteries but not in exercise mouse arteries, which exhibited greater ability to convert superoxide to HO Arteries from exercised mice exhibited less NOX II protein expression, more SOD isoform expression, and less sensitivity to ANG II. Endothelial cells subjected to laminar shear stress exhibited less NOX II subunit expression. In conclusion, aerobic exercise prevents high pressure-induced vascular dysfunction through an improved redox environment in the adipose microvasculature. We describe potential mechanisms contributing to aerobic exercise-conferred protection against high intravascular pressure. Subcutaneous adipose microvessels from exercise mice express less NADPH oxidase (NOX) II and more superoxide dismutase (SOD) and demonstrate less sensitivity to ANG II. In microvascular endothelial cells, shear stress reduced NOX II but did not influence SOD expression.

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Shear stress-induced mitochondrial biogenesis decreases the release of microparticles from endothelial cells

Cited by 61 publications

References 50 publications

Biogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK6

Biogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK6

Effect of exercise intensity on circulating microparticles in men and women

Short-term regular aerobic exercise reduces oxidative stress produced by acute high intraluminal pressure in the adipose microvasculature

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