Context‐dependent function of ROS in the vascular endothelium: The role of the Notch pathway and shear stress

Abstract

Reactive oxygen species (ROS) act as signal molecules in several biological processes whereas excessive, unregulated, ROS production contributes to the development of pathological conditions including endothelial dysfunction and atherosclerosis. The maintenance of a healthy endothelium depends on many factors and on their reciprocal interactions; in this framework, the Notch pathway and shear stress (SS) play two lead roles. Recently, evidence of a crosstalk between ROS, Notch, and SS, is emerging. The aim of this review is to describe the way ROS interact with the Notch pathway and SS protecting from-or promoting-the development of endothelial dysfunction. © 2017 BioFactors, 43(4):475-485, 2017.

The Use of Nutraceuticals to Counteract Atherosclerosis: The Role of the Notch Pathway

“…Interestingly, a diet rich in polyphenol powder, obtained from olive mill wastewater, enhanced antioxidant mechanisms and reduced oxidative stress-induced damage in chickens [33]. Moreover, in vitro treatment with hydroxytyrosol, or polyphenol extracts, from extra virgin olive oil, No prevention of heart attacks, strokes, or cardiovascular death [164] Reduced risk of CHD incidence 6 Oxidative Medicine and Cellular Longevity protects against the endothelial dysfunction induced by hyperglycemia and free fatty acids through modulation of NO production and endothelin-1 (ET-1) expression [34]. These observations have been confirmed by the NUTRAO-LEUM study, a randomized double-blind controlled trial, which supported the hypothesis of beneficial effects of virgin olive oils on biomarkers of endothelial dysfunction in healthy adults.…”

“…Additionally, by increasing the number of biomarkers of vascular function modified by nutraceuticals, the identification of "super responders" could be achieved, paving the way for "personalized nutraceutical treatments. " The Notch pathway, originally studied for its role in promoting the survival of cancer cells, is emerging as a key player in the maintenance of the vascular wall health and in the regulation of inflammation [5,6]. This pathway responds to agents, such as inflammatory cytokines and lipopolysaccharides, whose effects are contrasted by nutraceuticals.…”

“…Similarly, in human-induced pluripotent stem cell-(iPSC-) derived ECs, Notch-1 haploinsufficiency interferes with EC response to shear stress, causing the unlock of proosteogenic and inflammatory networks [253]. The interplay between Notch and shear stress is an emerging relevant topic in the context of vascular biology [6]. Diverse Notch signaling components in the endothelium respond to shear stress [254], and Notch-1 is essential for preserving EC tight junctions and their normal transcriptional/epigenetic response to shear stress [253,255].…”

Issue Highlights

“…Conversely, oscillatory blood flow induces aberrant ROS production, promoting endothelial dysfunction and atherosclerosis directly, or by inhibiting the Notch pathway. This interplay between blood flow conditions, ROS and Notch, as shown in the Figure, suggests the need to “personalize” the existing antioxidant therapies by assessing the levels of endothelial Notch .…”

Ticagrelor Increases SIRT1 and HES1 mRNA Levels in Peripheral Blood Cells from Patients with Stable Coronary Artery Disease and Chronic Obstructive Pulmonary Disease

“…Of interest, altered expression levels of Notch1 and its target gene HES1 have been associated to COPD [32,33]. The Notch pathway is regulated by cross-talks with a plethora of pathways [34,35] including the NAD + -dependent protein deacetylase, sirtuin1 (SIRT1), an oxidative stress sensor [36] and a repressor of inflammatory response [37], whose expression and activity is reduced in peripheral blood mononuclear cells (PBMCs) of stable CAD, ACS [38], and COPD [39] patients. Many studies have investigated the possible molecular mechanisms underlying the pleiotropic activity of ticagrelor in ACS [40][41][42][43] and SCAD [7] providing evidence of a ticagrelor-mediated increase in circulating levels of adenosine and cAMP [10,[44][45][46][47].…”