Interplay between Endoplasmic Reticulum Stress and Large Extracellular Vesicles (Microparticles) in Endothelial Cell Dysfunction

Abstract

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.

Raloxifene Ameliorates Glucosamine-Induced Insulin Resistance in Ovariectomized Rats

“…One study using a pancreatic β-cell line (INS-1 cells) demonstrated that RLX behaves as both an estrogen receptor antagonist through nuclear estrogen response element-dependent actions and as an estrogen receptor agonist by suppressing triglyceride accumulation [ 30 ]. The endoplasmic reticulum (ER) regulates intracellular calcium concentrations and protein folding and trafficking [ 31 , 32 , 33 , 34 ]. ER stress, the disruption of these ER functions, is related to T2DM in humans [ 35 , 36 , 37 ].…”

Short-Term High-Intensity Treadmill Exercise Promotes Ceramide-Dependent Extracellular Vesicle Secretion in the Central Nervous System of Mice

“…Our results provide a new perspective on the mechanism of exercise intervention. EVs in circulation are closely associated with multiple systems during physical activity and may include stem cell-derived vesicles, platelet-derived vesicles, pro-coagulant EVs, and cardiovascular-associated vesicles [ 21 , 28 - 30 ]. Further studies examining exercise-mediated EV release and EV-mediated signaling pathways may be useful for exploring new avenues for chronic disease treatment and clinical diagnosis [ 6 ].…”

Yoga Therapy Influence Onto Endothelium Function: Evidential Data

“…525 endothelial activation and damage. They are excreted from endotheliocytes in response to inflammation [22]. Hatha yoga training is proposed as prophylaxis of metabolic syndrome.…”