Onion and Apple Functional Ingredients Intake Improves Antioxidant and Inflammatory Status and Vascular Injury in Obese Zucker Rats.

The objective of this study was to investigate the effects of onion and apple functional ingredients in homozygous (fa/fa) obese Zucker rats. Rodents were fed three diets: standard diet [obese control (OC) group], standard diet containing 10% onion [obese onion 10% (OO) group] and standard diet containing 10% apple [obese apple 10% (OA) group] for 8 weeks. Food intake and body weight gain were higher in obese than in lean rats.

DPP4 Promotes Human Endothelial Cell Senescence and Dysfunction via the PAR2-COX-2-TP Axis and NLRP3 Inflammasome Activation.

Background: Abnormal accumulation of senescent cells in the vessel wall leads to a compromised vascular function contributing to vascular aging. Soluble DPP4 (dipeptidyl peptidase 4; sDPP4) secretion from visceral adipose tissue is enhanced in obesity, now considered a progeric condition. sDPP4 triggers vascular deleterious effects, albeit its contribution to vascular aging is unknown.

Pharmacological Blockade of NLRP3 Inflammasome/IL-1β-Positive Loop Mitigates Endothelial Cell Senescence and Dysfunction.

The clinical relevance of IL-1β in chronic inflammation underlying atherosclerosis has been reinforced by recent evidence associating pharmacological inhibition of the cytokine with lower cardiovascular risk. Previously, we have demonstrated a direct involvement of IL-1β in endothelial senescence. Therefore, this can be a key mechanism contributing to the sterile inflammatory milieu associated with aging, termed inflammaging.

Visfatin/eNampt induces endothelial dysfunction in vivo: a role for Toll-Like Receptor 4 and NLRP3 inflammasome.

Visfatin/extracellular-nicotinamide-phosphoribosyltranferase-(eNampt) is a multifaceted adipokine enhanced in type-2-diabetes and obesity. Visfatin/eNampt cause in vitro endothelial dysfunction and vascular inflammation, although whether the same effects are achieved in vivo is unknown. Toll-like receptor-4 (TLR4), a main surface pattern recognition receptor of innate immune system is a potential target for visfatin/eNampt.

The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation.

Endothelial cell senescence is a hallmark of vascular aging that predisposes to vascular disease. We aimed to explore the capacity of the renin-angiotensin system (RAS) heptapeptide angiotensin (Ang)-(1-7) to counteract human endothelial cell senescence and to identify intracellular pathways mediating its potential protective action. In human umbilical vein endothelial cell (HUVEC) cultures, Ang II promoted cell senescence, as revealed by the enhancement in senescence-associated galactosidase (SA-β-gal+) positive staining, total and telomeric DNA damage, adhesion molecule expression, and human mononuclear adhesion to HUVEC monolayers.

Genome-Wide Inhibition of Pro-atherogenic Gene Expression by Multi-STAT Targeting Compounds as a Novel Treatment Strategy of CVDs.

Cardiovascular diseases (CVDs), including atherosclerosis, are globally the leading cause of death. Key factors contributing to onset and progression of atherosclerosis include the pro-inflammatory cytokines Interferon (IFN)α and IFNγ and the Pattern Recognition Receptor (PRR) Toll-like receptor 4 (TLR4). Together, they trigger activation of Signal Transducer and Activator of Transcription (STAT)s.

Dual Effects of Resveratrol on Cell Death and Proliferation of Colon Cancer Cells.

Colorectal cancer remains a main cause of deaths worldwide, and novel agents are being searched to treat this disease. Polyphenols have emerged as promising therapeutic tools in cancer. Resveratrol (3,5,4'-trihydoxy-trans-stilbene) induces cell death in different tumor cell lines, and it also stimulates the proliferation of specific breast and prostate cancer cell lines.

Role of glutathione biosynthesis in endothelial dysfunction and fibrosis.

Glutathione (GSH) biosynthesis is essential for cellular redox homeostasis and antioxidant defense. The rate-limiting step requires glutamate-cysteine ligase (GCL), which is composed of the catalytic (GCLc) and the modulatory (GCLm) subunits. To evaluate the contribution of GCLc to endothelial function we generated an endothelial-specific Gclc haplo-insufficient mouse model (Gclc e/+ mice).

Mas receptor is involved in the estrogen-receptor induced nitric oxide-dependent vasorelaxation.

The Mas receptor is involved in the angiotensin (Ang)-(1-7) vasodilatory actions by increasing nitric oxide production (NO). We have previously demonstrated an increased production of Ang-(1-7) in human umbilical vein endothelial cells (HUVEC) exposed to estradiol (E2), suggesting a potential cross-talk between E2 and the Ang-(1-7)/Mas receptor axis. Here, we explored whether the vasoactive response and NO-related signalling exerted by E2 are influenced by Mas.

The Angiotensin-(1-7)/Mas Axis Counteracts Angiotensin II-Dependent and -Independent Pro-inflammatory Signaling in Human Vascular Smooth Muscle Cells.

Targeting inflammation is nowadays considered as a challenging pharmacological strategy to prevent or delay the development of vascular diseases. Angiotensin-(1-7) is a member of the renin-angiotensin system (RAS) that binds Mas receptors and has gained growing attention in the last years as a regulator of vascular homeostasis. Here, we explored the capacity of Ang-(1-7) to counteract human aortic smooth muscle cell (HASMC) inflammation triggered by RAS-dependent and -independent stimuli, such as Ang II or interleukin (IL)-1β.

Soluble dipeptidyl peptidase-4 induces microvascular endothelial dysfunction through proteinase-activated receptor-2 and thromboxane A2 release.

Background: Dipeptidyl peptidase-4 (DPP4) is a key protein in glucose homeostasis and a pharmacological target in type 2 diabetes mellitus. This study explored whether the novel adipokine soluble DPP4 (sDPP4) can cause endothelial dysfunction, an early marker of impaired vascular reactivity.

Method: Reactivity was studied in mesenteric arteries from 3-month-old female mice, using a small vessel myograph.

The interleukin-1 receptor antagonist anakinra improves endothelial dysfunction in streptozotocin-induced diabetic rats.

Background: Endothelial dysfunction is a crucial early phenomenon in vascular diseases linked to diabetes mellitus and associated to enhanced oxidative stress. There is increasing evidence about the role for pro-inflammatory cytokines, like interleukin-1β (IL-1β), in developing diabetic vasculopathy. We aimed to determine the possible involvement of this cytokine in the development of diabetic endothelial dysfunction, analysing whether anakinra, an antagonist of IL-1 receptors, could reduce this endothelial alteration by interfering with pro-oxidant and pro-inflammatory pathways into the vascular wall.

Endothelial C-type natriuretic peptide maintains vascular homeostasis.

The endothelium plays a fundamental role in maintaining vascular homeostasis by releasing factors that regulate local blood flow, systemic blood pressure, and the reactivity of leukocytes and platelets. Accordingly, endothelial dysfunction underpins many cardiovascular diseases, including hypertension, myocardial infarction, and stroke. Herein, we evaluated mice with endothelial-specific deletion of Nppc, which encodes C-type natriuretic peptide (CNP), and determined that this mediator is essential for multiple aspects of vascular regulation.

High-cholesterol diet enriched with onion affects endothelium-dependent relaxation and NADPH oxidase activity in mesenteric microvessels from Wistar rats.

Background: The aim of the present study was to examine the effects of onion as functional ingredient on the oxidative status, lipoprotein levels (total cholesterol-TC, HDL-C, LDL-C), triacylglycerides (TAG) and vascular reactivity of mesenteric arteries in hypercholesterolemic Wistar rats.

Methods: Twenty-four animals were fed with three different diets [control, high-cholesterol diet (HC) and high-cholesterol enriched with onion diet (HCO)]. After seven weeks of experimental feeding the rats were euthanized for blood and tissues collection.

Complete blockade of the vasorelaxant effects of angiotensin-(1-7) and bradykinin in murine microvessels by antagonists of the receptor Mas.

The heptapeptide angiotensin-(1-7) is a biologically active metabolite of angiotensin II, the predominant peptide of the renin-angiotensin system. Recently, we have shown that the receptor Mas is associated with angiotensin-(1-7)-induced signalling and mediates, at least in part, the vasodilatory properties of angiotensin-(1-7). However, it remained controversial whether an additional receptor could account for angiotensin-(1-7)-induced vasorelaxation.

Characterization of endothelium-dependent relaxations in the mesenteric vasculature: a comparative study with potential pathophysiological relevance.

Background: Endothelium-dependent relaxations in human adult mesenteric microvessels involve 3 different main mechanisms: cyclooxygenase (COX)-derived prostanoids, nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF), which elicits vascular smooth muscle hyperpolarization and relaxation. There are some pathological conditions with an abnormal balance between mesenteric vasoconstriction and vasodilatation inputs leading to endothelial dysfunction and tissue injury.

Purpose: The purpose was to characterize the mechanisms mediating endothelium-dependent relaxation and differences in children and adult mesenteric microvessels.

Mechanisms involved in the aging-induced vascular dysfunction.

Vascular aging is a key process determining health status of aged population. Aging is an independent cardiovascular risk factor associated to an impairment of endothelial function, which is a very early and important event leading to cardiovascular disease. Vascular aging, formerly being considered an immutable and inexorable risk factor, is now viewed as a target process for intervention in order to achieve a healthier old age.

Age-related differences in the effects of α and γ peroxisome proliferator-activated receptor subtype agonists on endothelial vasodilation in human microvessels.

Endothelial vasodilation in human vessels is impaired by aging and other cardiovascular risk factors (CVRF) but the differential impact of aging and CVRF in human endothelial function is not completely elucidated. The aim of this work was to evaluate the influence of aging on the effects of peroxisome proliferator-activated receptor (PPAR)-α and -γ subtype agonists on endothelium-dependent vasodilation of isolated human vessels from subjects with or without CVRF. Human mesenteric microarteries were dissected from omentum specimens obtained from subjects younger or older than 60 years having or not CVRF and mounted in wire myographs to evaluate endothelium-dependent relaxation to bradykinin (BK).

Visfatin impairs endothelium-dependent relaxation in rat and human mesenteric microvessels through nicotinamide phosphoribosyltransferase activity.

Visfatin, also known as extracellular pre-B-cell colony-enhancing factor (PBEF) and nicotinamide phosphoribosyltransferase (Nampt), is an adipocytokine whose circulating levels are enhanced in metabolic disorders, such as type 2 diabetes mellitus and obesity. Circulating visfatin levels have been positively associated with vascular damage and endothelial dysfunction. Here, we investigated the ability of visfatin to directly impair vascular reactivity in mesenteric microvessels from both male Sprague-Dawley rats and patients undergoing non-urgent, non-septic abdominal surgery.

Pathways responsible for apoptosis resulting from amadori-induced oxidative and nitrosative stress in human mesothelial cells.

Background: Apoptosis and inflammatory/oxidative stress have been associated with hyperglycemia in human peritoneal mesothelial cells (HPMCs) and other cell types. We and others have highlighted the role of early products of non-enzymatic protein glycation in inducing proinflammatory conditions and increasing apoptotic rates in HPMCs. Loss of HPMCs seems to be a hallmark of complications associated with peritoneal membrane dysfunction.

Endothelial dysfunction in aged humans is related with oxidative stress and vascular inflammation.

Vascular endothelial dysfunction occurs during the human aging process, and it is considered as a crucial event in the development of many vasculopathies. We investigated the underlying mechanisms of this process, particularly those related with oxidative stress and inflammation, in the vasculature of subjects aged 18-91 years without cardiovascular disease or risk factors. In isolated mesenteric microvessels from these subjects, an age-dependent impairment of the endothelium-dependent relaxations to bradykinin was observed.

Rats surviving injurious mechanical ventilation show reversible pulmonary, vascular and inflammatory changes.

Objective: To describe the time course of the changes in pulmonary and vascular function, and systemic inflammation induced by injurious mechanical ventilation.

Design: Experimental study in an animal model of ventilator-induced lung injury.

Setting: Animal research laboratory.

Endothelial dysfunction through genetic deletion or inhibition of the G protein-coupled receptor Mas: a new target to improve endothelial function.

Background: Endothelial dysfunction is an initial step in the pathogenesis of cardiovascular diseases. Since we previously identified the G protein-coupled receptor Mas as a receptor for angiotensin (Ang)-(1-7), a heptapeptide with endothelium-dependent vasorelaxant properties, we investigated whether alterations on the Ang-(1-7)/Mas axis alter endothelial function.

Results: Ang-(1-7)-mediated relaxation of murine wild-type mesenteric arteries was equally impaired in both wild-type arteries pretreated with the Ang-(1-7) receptor blocker, A779, and arteries isolated from Mas-deficient mice.

Amadori adducts activate nuclear factor-kappaB-related proinflammatory genes in cultured human peritoneal mesothelial cells.

Diabetes mellitus leads to a high incidence of several so-called complications, sharing similar pathophysiological features in several territories. Previous reports points at early nonenzymatic glycosylation products (Amadori adducts) as mediators of diabetic vascular complications. In the present study, we analysed a possible role for Amadori adducts as stimulators of proinflammatory pathways in human peritoneal mesothelial cells (HPMCs).

Glycosylated human oxyhaemoglobin activates nuclear factor-kappaB and activator protein-1 in cultured human aortic smooth muscle.

Diabetic vessels undergo structural changes that are linked to a high incidence of cardiovascular diseases. Reactive oxygen species (ROS) mediate cell signalling in the vasculature, where they can promote cell growth and activate redox-regulated transcription factors, like activator protein-1 (AP-1) or nuclear factor-kappaB (NF-kappaB), which are involved in remodelling and inflammation processes. Amadori adducts, formed through nonenzymatic glycosylation, can contribute to ROS formation in diabetes.