Endothelial mechanotransduction proteins and vascular function are altered by dietary sucrose supplementation in healthy young male subjects

Abstract

Endothelial mechanotransduction is important for vascular function but alterations and activation of vascular mechanosensory proteins have not been investigated in humans. In endothelial cell culture, simple sugars effectively impair mechanosensor proteins. To study mechanosensor- and vascular function in humans, 12 young healthy male subjects supplemented their diet with 3 × 75 g sucrose day for 14 days in a randomized cross-over design. Before and after the intervention period, the hyperaemic response to passive lower leg movement and active knee extensor exercise was determined by ultrasound doppler. A muscle biopsy was obtained from the thigh muscle before and after acute passive leg movement to allow assessment of protein amounts and the phosphorylation status of mechanosensory proteins and NADPH oxidase. The sucrose intervention led to a reduced flow response to passive movement (by 17 ± 2%) and to 12 W of active exercise (by 9 ± 1%), indicating impaired vascular function. A reduced flow response to passive and active exercise was paralleled by a significant up-regulation of platelet endothelial cell adhesion molecule (PECAM-1), endothelial nitric oxide synthase, NADPH oxidase and the Rho family GTPase Rac1 protein expression in the muscle tissue, as well as an increased basal phosphorylation status of vascular endothelial growth factor receptor 2 and a reduced phosphorylation status of PECAM-1. The phosphorylation status was not acutely altered with passive leg movement. These findings indicate that a regular intake of high levels of sucrose can impair vascular mechanotransduction and increase the oxidative stress potential, and suggest that dietary excessive sugar intake may contribute to the development of vascular disease.

Impact of pre‐exercise feeding status on metabolic adaptations to endurance‐type exercise training

“…First, there is an increase in skeletal muscle glucose uptake to help satisfy the higher energy demands of the activity. Each bout of exercise performed activates AMP-activated protein kinase (AMPK), Akt substrate of 160 kDa (AS160/TBC1D4) (Treebak et al 2009;Herzig & Shaw, 2018), Rac1 (Gliemann et al 2017) and Ca 2+ /calmodulin-dependent protein kinase II (Witczak et al 2010) pathways within skeletal muscle, which induces the translocation of the glucose transporter type 4 (GLUT4) protein to the plasma membrane and the t-tubules to facilitate increased transmembrane glucose transport (Hawley & Lessard, 2008). Together with increased microvascular perfusion, these mechanisms contribute to increased peripheral insulin sensitivity and skeletal muscle glucose uptake in the acute post-exercise period (Sjøberg et al 2017;Hingst et al 2018).…”

Impact of Nutritional Epigenetics in Essential Hypertension: Targeting microRNAs in the Gut-Liver Axis

“…A study by Wu et al demonstrates that AGE can suppress miR-200b and miR-200c, leading to unregulated RhoA/ROCK2 signaling during endothelial injury [ 87 ]; however, whether this relates to EH etiology remains unknown. Thus, the role of elevated AGE [ 88 ] and/or impaired endothelial mechanotransduction [ 89 ] as a result of dietary sugar consumption needs further investigation in EH. Noteworthy is that chronic ingestion of sucrose reportedly increased circulatory miR-21 and miR-223 [ 90 ].…”

Cytoskeletal Remodeling Mimics Endothelial Response to Microgravity

“…Consequently, while a healthy endothelium is fundamental for mammalian survival, endothelial dysfunction is at the roots of many diseases ( Drexler and Hornig, 1999 ; Vanhoutte et al, 2017 ; Sun et al, 2019 ; Morris et al, 2020 ; Siddiqi et al, 2021 ). EC sense and react to mechanical stimuli through complex pathways that translate mechanical forces into biochemical signals that ultimately carve cell phenotype and function ( Gliemann et al, 2017 ). The endothelium is exposed simultaneously to three types of mechanical forces: shear stress, circumferential strain, and, although often forgotten, gravity.…”