scholarly journals Modulation of endothelial cell phenotype by physical activity: impact on obesity-related endothelial dysfunction

2015 ◽  
Vol 309 (1) ◽  
pp. H1-H8 ◽  
Author(s):  
Shawn B. Bender ◽  
M. Harold Laughlin

Increased levels of physical activity are associated with reduced cardiovascular disease (CVD) risk and mortality in obesity and diabetes. Available evidence suggests that local factors, including local hemodynamics, account for a significant portion of this CVD protection, and numerous studies have interrogated the therapeutic benefit of physical activity/exercise training in CVD. Less well established is whether basal differences in endothelial cell phenotype between/among vasculatures related to muscle recruitment patterns during activity may account for reports of nonuniform development of endothelial dysfunction in obesity. This is the focus of this review. We highlight recent work exploring the vulnerability of two distinct vasculatures with established differences in endothelial cell phenotype. Specifically, based largely on dramatic differences in underlying hemodynamics, arteries perfusing soleus muscle (slow-twitch muscle fibers) and those perfusing gastrocnemius muscle (fast-twitch muscle fibers) in the rat exhibit an exercise training-like versus an untrained endothelial cell phenotype, respectively. In the context of obesity, therefore, arteries to soleus muscle exhibit protection from endothelial dysfunction compared with vulnerable arteries to gastrocnemius muscle. This disparate vulnerability is consistent with numerous animal and human studies, demonstrating increased skeletal muscle blood flow heterogeneity in obesity coincident with reduced muscle function and exercise intolerance. Mechanistically, we highlight emerging areas of inquiry exploring novel aspects of hemodynamic-sensitive signaling in endothelial cells and the time course of physical activity-associated endothelial adaptations. Lastly, further exploration needs to consider the impact of endothelial heterogeneity on the development of endothelial dysfunction because endothelial dysfunction independently predicts CVD events.

2021 ◽  
Vol 18 (4) ◽  
pp. 147916412110290
Author(s):  
Jie Zheng ◽  
Christopher Sorensen ◽  
Ran Li ◽  
Hongyu An ◽  
Charles F Hildebolt ◽  
...  

Objective: To evaluate regional calf muscle microcirculation in people with diabetes mellitus (DM) with and without foot ulcers, compared to healthy control people without DM, using contrast-free magnetic resonance imaging methods. Methods: Three groups of subjects were recruited: non-DM controls, DM, and DM with foot ulcers (DM + ulcer), all with ankle brachial index (ABI) > 0.9. Skeletal muscle blood flow (SMBF) and oxygen extraction fraction (SMOEF) in calf muscle were measured at rest and during a 5-min isometric ankle plantarflexion exercise. Subjects completed the Yale physical activity survey. Results: The exercise SMBF (ml/min/100 g) of the medial gastrocnemius muscle were progressively impaired: 63.7 ± 18.9 for controls, 42.9 ± 6.7 for DM, and 36.2 ± 6.2 for DM + ulcer, p < 0.001. Corresponding exercise SMOEF was the lowest in DM + ulcers (0.48 ± 0.09). Exercise SMBF in the soleus muscle was correlated moderately with the Yale physical activity survey ( r = 0.39, p < 0.01). Conclusions: Contrast-free MR imaging identified progressively impaired regional microcirculation in medial gastrocnemius muscles of people with DM with and without foot ulcers. Exercise SMBF in the medial gastrocnemius muscle was the most sensitive index and was associated with HbA1c. Lower exercise SMBF in the soleus muscle was associated with lower Yale score.


2010 ◽  
Vol 299 (2) ◽  
pp. H379-H385 ◽  
Author(s):  
Jaume Padilla ◽  
Sean C. Newcomer ◽  
Grant H. Simmons ◽  
Kurt V. Kreutzer ◽  
M. Harold Laughlin

Although the beneficial effects of exercise training on conduit artery endothelial function are well-established in animals and humans with compromised basal function, whether exercise exerts favorable effects on a healthy endothelium is inconclusive. We sought to determine whether long-term exercise training enhances endothelial function in peripheral conduit arteries of healthy pigs. Using a retrospective analysis of data collected in our laboratory ( n = 127), we compared in vitro brachial and femoral artery endothelium-dependent and -independent relaxation between a group of pigs that exercise-trained for 16–20 wk and a group that remained sedentary. No differences in vasomotor function were found between the 2 groups ( P > 0.05). Additionally, in a subset of pigs ( n = 16), expression levels of 18 proteins that are typically associated with the atherosclerotic process were measured by immunoblot analysis of endothelial cell scrapes obtained from the brachial and femoral arteries. We found no differences ( P > 0.05) in endothelial gene expression between these exercise-trained and sedentary healthy pigs. These results indicate that pigs exhibiting the classic training-induced adaptations do not demonstrate enhanced endothelium-dependent dilation nor reveal a more atheroprotected endothelial cell phenotype in their brachial and femoral arteries than their sedentary but otherwise healthy counterparts.


Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 409
Author(s):  
Aisha Osman ◽  
Tarek Benameur ◽  
Hesham M. Korashy ◽  
Asad Zeidan ◽  
Abdelali Agouni

Upon increased demand for protein synthesis, accumulation of misfolded and/or unfolded proteins within the endoplasmic reticulum (ER), a pro-survival response is activated termed unfolded protein response (UPR), aiming at restoring the proper function of the ER. Prolonged activation of the UPR leads, however, to ER stress, a cellular state that contributes to the pathogenesis of various chronic diseases including obesity and diabetes. ER stress response by itself can result in endothelial dysfunction, a hallmark of cardiovascular disease, through various cellular mechanisms including apoptosis, insulin resistance, inflammation and oxidative stress. Extracellular vesicles (EVs), particularly large EVs (lEVs) commonly referred to as microparticles (MPs), are membrane vesicles. They are considered as a fingerprint of their originating cells, carrying a variety of molecular components of their parent cells. lEVs are emerging as major contributors to endothelial cell dysfunction in various metabolic disease conditions. However, the mechanisms underpinning the role of lEVs in endothelial dysfunction are not fully elucidated. Recently, ER stress emerged as a bridging molecular link between lEVs and endothelial cell dysfunction. Therefore, in the current review, we summarized the roles of lEVs and ER stress in endothelial dysfunction and discussed the molecular crosstalk and relationship between ER stress and lEVs in endothelial dysfunction.


2005 ◽  
Vol 30 (4) ◽  
pp. 442-474 ◽  
Author(s):  
James W.E. Rush ◽  
Steven G. Denniss ◽  
Drew A. Graham

Cardiovascular disease is the single leading cause of death and morbidity for Canadians. A universal feature of cardiovascular disease is dysfunction of the vascular endothelium, thus disrupting control of vasodilation, tissue perfusion, hemostasis, and thrombosis. Nitric oxide bioavailability, crucial for maintaining vascular endothelial health and function, depends on the processes controlling synthesis and destruction of nitric oxide as well as on the sensitivity of target tissue to nitric oxide. Evidence supports a major contribution by oxidative stress-induced destruction of nitric oxide to the endothelial dysfunction that accompanies a number of cardiovascular disease states including hypertension, diabetes, chronic heart failure, and atherosclerosis. Regular physical activity (exercise training) reduces cardiovascular disease risk. Numerous studies support the hypothesis that exercise training improves vascular endothelial function, especially when it has been impaired by preexisting risk factors. Evidence is emerging to support a role for improved nitric oxide bioavailability with training as a result of enhanced synthesis and reduced oxidative stress-mediated destruction. Molecular targets sensitive to the exercise training effect include the endothelial nitric oxide synthase and the antioxidant enzyme superoxide dismutase. However, many fundamental details of the cellular and molecular mechanisms linking exercise to altered molecular and functional endothelial phenotypes have yet to be discovered. The working hypothesis is that some of the cellular mechanisms contributing to endothelial dysfunction in cardiovascular disease can be targeted and reversed by signals associated with regular increases in physical activity. The capacity for exercise training to regulate vascular endothelial function, nitric oxide bioavailability, and oxidative stress is an example of how lifestyle can complement medicine and pharmacology in the prevention and management of cardiovascular disease. Key words: exercise, artery, reactive oxygen species, antioxidant, hypertension


2022 ◽  
Vol 9 ◽  
Author(s):  
Derek L. Tran ◽  
Hannah Gibson ◽  
Andrew J. Maiorana ◽  
Charlotte E. Verrall ◽  
David W. Baker ◽  
...  

Background: Despite developments in surgical techniques and medical care, people with a Fontan circulation still experience long-term complications; non-invasive therapies to optimize the circulation have not been established. Exercise intolerance affects the majority of the population and is associated with worse prognosis. Historically, people living with a Fontan circulation were advised to avoid physical activity, but a small number of heterogenous, predominantly uncontrolled studies have shown that exercise training is safe—and for unique reasons, may even be of heightened importance in the setting of Fontan physiology. The mechanisms underlying improvements in aerobic exercise capacity and the effects of exercise training on circulatory and end-organ function remain incompletely understood. Furthermore, the optimal methods of exercise prescription are poorly characterized. This highlights the need for large, well-designed, multi-center, randomized, controlled trials.Aims and Methods: The Fontan Fitness Intervention Trial (F-FIT)—a phase III clinical trial—aims to optimize exercise prescription and delivery in people with a Fontan circulation. In this multi-center, randomized, controlled study, eligible Fontan participants will be randomized to either a 4-month supervised aerobic and resistance exercise training program of moderate-to-vigorous intensity followed by an 8-month maintenance phase; or usual care (control group). Adolescent and adult (≥16 years) Fontan participants will be randomized to either traditional face-to-face exercise training, telehealth exercise training, or usual care in a three-arm trial with an allocation of 2:2:1 (traditional:telehealth:control). Children (&lt;16 years) will be randomized to either a physical activity and exercise program of moderate-to-vigorous intensity or usual care in a two-arm trial with a 1:1 allocation. The primary outcome is a change in aerobic exercise capacity (peak oxygen uptake) at 4-months. Secondary outcomes include safety, and changes in cardiopulmonary exercise testing measures, peripheral venous pressure, respiratory muscle and lung function, body composition, liver stiffness, neuropsychological and neurocognitive function, physical activity levels, dietary and nutritional status, vascular function, neurohormonal activation, metabolites, cardiac function, quality of life, musculoskeletal fitness, and health care utilization. Outcome measures will be assessed at baseline, 4-months, and 12-months. This manuscript will describe the pathophysiology of exercise intolerance in the Fontan circulation and the rationale and protocol for the F-FIT.


2020 ◽  
Vol 29 (3) ◽  
pp. 208-213
Author(s):  
Kangil Lim ◽  
Kijeong Kim

PURPOSE: The physiological role of adipocytokines on obesity, diabetes, and insulin resistance is not clearly understood yet. Furthermore, the mechanism of exercise-induced changes in plasma adiponectin in obesity and diabetes is not known well. The aim of this review is to describe the role of exercise on the adiponectin production in adipose tissue of the obesity and diabetes.METHODS: This study reviews 46 previous studies focusing on the effect of exercise on adiponectin in obese and diabetic individuals.RESULTS: Increasing adiponectin levels after long-term exercise training in obese and diabetic individuals have inconsistent support in the scientific literature. However, the present review summarized evidence that supports for exercise training as a viable strategy to increase adiponectin in obese and diabetic individuals.CONCLUSIONS: Despite the importance of regular physical activity for the prevention of obesity and diabetes outlined in numerous guidelines and recommendations, previous studies showed inconsistent results regarding the effect of physical activity among obese and diabetic individuals. This review suggested that exercise training induces the augmentation of the anti-inflammatory cytokine adiponectin and in turn, it provides long-term health outcomes for obese and diabetic individuals.


2019 ◽  
Vol 25 (1) ◽  
pp. 17-22
Author(s):  
I.S. Dronyk ◽  
◽  
O.Y. Yavorsky ◽  
O.Y. Sklyarov ◽  
R.S. Pshyk ◽  
...  

2020 ◽  
Vol 9 (02) ◽  
pp. 153-165
Author(s):  
François Carré

AbstractThe benefits of regular physical activity whether in primary- or secondary prevention of cardiovascular disease are now irrefutable. Despite its well proven benefits, exercise training remains underused because of lack of insight and familiarity of the majority of cardiologists. This review offers cardiologists the necessary informations about the pathophysiological mechanisms, effects and limitations of the predominantly used training methods in various kardiovascular diseases.


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