Provinols™, a Polyphenolic Extract of Red Wine, Inhibits In-Stent Neointimal Growth in Cholesterol-Fed Rabbit.

Epidemiological studies indicate a potential correlation between the consumption of polyphenols and a reduced risk of developing cardiovascular disorders. The present study investigates the potential of a red wine polyphenol oral extract, Provinols™, to reduce neointimal hyperplasia following angioplasty in a hypercholesterolemic rabbit model. New Zealand white rabbits were fed 1% cholesterol-enriched chow for a period of eight weeks prior to the induction of iliac balloon injury and subsequent stent placement.

Circulating extracellular vesicle-carried PTP1B and PP2A phosphatases as regulators of insulin resistance.

Aims/hypothesis: Metabolic disorders associated with abdominal obesity, dyslipidaemia, arterial hypertension and hyperglycaemia are risk factors for the development of insulin resistance. Extracellular vesicles (EVs) may play an important role in the regulation of metabolic signalling pathways in insulin resistance and associated complications.

Methods: Circulating large EVs (lEVs) and small EVs (sEVs) from individuals with (IR group) and without insulin resistance (n-IR group) were isolated and characterised.

Small Extracellular Vesicles Harboring PD-L1 in Obstructive Sleep Apnea.

Obstructive sleep apnea syndrome (OSA) has been associated with increased cancer incidence and aggressiveness. One hypothesis to support this association is the implication of immune response, particularly the programmed cell death pathway, formed by the receptor PD-1 and its ligand PD-L1. Recent studies have shown dysregulation of this pathway in severe OSA patients.

Biotherapeutic approaches against cardio-metabolic dysfunctions based on extracellular vesicles.

Among the different pathways involved in the cell-to-cell communication, extracellular vesicles (EVs) are defined as key players in the transport of different signalling molecules, such as lipids, proteins, and RNA, from the originating cells to specific target cells. The biogenesis and composition of EVs are complex and confer them a unique ability to more effectively reach tissues and cells as compared to other types of synthetic carriers. Owing to these properties, EVs have been suggested as new therapeutic tools for personalized medicine.

Mesenchymal stem cell-derived extracellular vesicles exert pro-angiogenic and pro-lymphangiogenic effects in ischemic tissues by transferring various microRNAs and proteins including ITGa5 and NRP1.

Mesenchymal stem cells/stromal cells (MSCs)-derived extracellular vesicles (EVs) mediate pro-regenerative effects in damaged ischemic tissues by regulating angiogenesis. MSCs-EVs modulate functions of cells including endogenous mature cells, progenitors and stem cells, resulting in restoration of blood flow. However, the mechanisms underlying such MSC-EV activity still remain poorly understood.

'Yapping' with extracellular vesicles in fatty liver metastasis.

Liver metastasis is a major cause of death in patients with colorectal cancer (CRC). A recent study by Wang et al. has deciphered unprecedented prometastatic and immunosuppressive properties of the tumor microenvironment (TME) mediated by hepatocyte-derived extracellular vesicles (EVs) in fatty liver, paving the way for therapeutic innovations to treat patients with CRC and liver metastasis.

Faeces-derived extracellular vesicles participate in the onset of barrier dysfunction leading to liver diseases.

The role of extracellular vesicles (EVs) from faeces (fEVs) and small circulating EVs (cEVs) in liver diseases such as non-alcoholic fatty diseases (NAFLD) and non-alcoholic steatohepatitis (NASH) has not been demonstrated. fEVs and cEVs of healthy donors, NAFLD and NASH patients were isolated and characterized. The effects of EVs were evaluated in intestinal, endothelial, Kupffer and stellate cells.

Small extracellular vesicle targeting of hypothalamic AMPKα1 promotes weight loss in leptin receptor deficient mice.

Background And Aims: Leptin receptor (LEPR) deficiency promotes severe obesity and metabolic disorders. However, the current therapeutic options against this syndrome are scarce.

Methods: db/db mice and their wildtypes were systemically treated with neuronal-targeted small extracellular vesicles (sEVs) harboring a plasmid encoding a dominant negative mutant of AMP-activated protein kinase alpha 1 (AMPKα1-DN) driven by steroidogenic factor 1 (SF1) promoter; this approach allowed to modulate AMPK activity, specifically in SF1 cells of the ventromedial nucleus of the hypothalamus (VMH).

Enhancement of the In Vitro Antitumor Effects of Berberine Chloride When Encapsulated within Small Extracellular Vesicles.

Berberine hydrochloride (BRB) is an isoquinoline alkaloid with promising anticancer efficacies. However, application of BRB had been hampered by its poor aqueous solubility, low gastrointestinal absorption, and rapid metabolism. The present study takes advantage of small extracellular vesicles (sEVs) to increase both stability and efficacy of BRB.

At the crossroads of fertility and metabolism: the importance of AMPK-dependent signaling in female infertility associated with hyperandrogenism.

Study Question: What biological processes are linked to the signaling of the energy sensor 5'-AMP-activated protein kinase (AMPK) in mouse and human granulosa cells (GCs)?

Summary Answer: The lack of α1AMPK in GCs impacted cell cycle, adhesion, lipid metabolism and induced a hyperandrogenic response.

What Is Known Already: AMPK is expressed in the ovarian follicle, and its activation by pharmacological medications, such as metformin, inhibits the production of steroids. Polycystic ovary syndrome (PCOS) is responsible for infertility in approximately 5-20% of women of childbearing age and possible treatments include reducing body weight, improving lifestyle and the administration of a combination of drugs to improve insulin resistance, such as metformin.

Understanding the Effects of Antipsychotics on Appetite Control.

Antipsychotic drugs (APDs) represent a cornerstone in the treatment of schizophrenia and other psychoses. The effectiveness of the first generation (typical) APDs are hampered by so-called extrapyramidal side effects, and they have gradually been replaced by second (atypical) and third-generation APDs, with less extrapyramidal side effects and, in some cases, improved efficacy. However, the use of many of the current APDs has been limited due to their propensity to stimulate appetite, weight gain, and increased risk for developing type 2 diabetes and cardiovascular disease in this patient group.

Enhancement of the Anti-Angiogenic Effects of Delphinidin When Encapsulated within Small Extracellular Vesicles.

(1) Background: The anthocyanin delphinidin exhibits anti-angiogenic properties both in in vitro and in vivo angiogenesis models. However, in vivo delphinidin is poorly absorbed, thus its modest bioavailability and stability reduce its anti-angiogenic effects. The present work takes advantage of small extracellular vesicle (sEV) properties to enhance both the stability and efficacy of delphinidin.

Carrot Supplementation Improves Blood Pressure and Reduces Aortic Root Lesions in an Atherosclerosis-Prone Genetic Mouse Model.

Epidemiological studies have shown that carrot consumption may be associated with a lower risk of developing several metabolic dysfunctions. Our group previously determined that the Bolero (Bo) carrot variety exhibited vascular and hepatic tropism using cellular models of cardiometabolic diseases. The present study evaluated the potential metabolic and cardiovascular protective effect of Bo, grown under two conditions (standard and biotic stress conditions (BoBS)), in apolipoprotein E-knockout (ApoE) mice fed with high fat diet (HFD).

LPS-enriched small extracellular vesicles from metabolic syndrome patients trigger endothelial dysfunction by activation of TLR4.

Background: Metabolic syndrome (MetS) is characterized by a cluster of interconnected risk factors -hyperglycemia, dyslipidemia, hypertension and obesity- leading to an increased risk of cardiovascular events. Small extracellular vesicles (sEVs) can be considered as new biomarkers of different pathologies, and they are involved in intercellular communication. Here, we hypothesize that sEVs are implicated in MetS-associated endothelial dysfunction.

Bacterial and eukaryotic extracellular vesicles and nonalcoholic fatty liver disease: new players in the gut-liver axis?

The liver and intestine communicate in a bidirectional way through the biliary tract, portal vein, and other components of the gut-liver axis. The gut microbiota is one of the major contributors to the production of several proteins and bile acids. Imbalance in the gut bacterial community, called dysbiosis, participates in the development and progression of several chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD).

Intermittent Hypoxia Mediates Caveolae Disassembly That Parallels Insulin Resistance Development.

Repetitive complete or incomplete pharyngeal collapses are leading to chronic intermittent hypoxia (CIH), a hallmark feature of obstructive sleep apnea (OSA) syndrome responsible for many metabolic disorders. In humans, an association between OSA and insulin resistance has been found independently of the degree of obesity. Based on our previous work showing that hypoxia applied to adipocytes led to cellular insulin resistance associated with caveolae flattening, we have investigated the effects of CIH on caveolae structuration in adipose tissue.

Microbiota-derived extracellular vesicles and metabolic syndrome.

Aim: Metabolic syndrome is a major health problem concerning approximately 25% of worldwide population. Metabolic syndrome regroups a cluster of five metabolic abnormalities predisposing to Type 2 Diabetes mellitus. Dysbiotic gut microbiota is accompanied by an increase of both intestinal permeability and pathogen-associated molecular patterns translocation into blood circulation to induce metabolic endotoxemia responsible for the low-grade systemic inflammation and insulin resistance in metabolic syndrome.

Apple Supplementation Improves Hemodynamic Parameter and Attenuates Atherosclerosis in High-Fat Diet-Fed Apolipoprotein E-Knockout Mice.

Epidemiological studies describe the association between apple consumption and improved cardiovascular and metabolic dysfunction. Our recent multiparametric screening on cellular model studies has shown that apples exhibit vascular tropism including Granny Smith (GS) variety independently of the storage condition. The present study aimed to evaluate the cardiovascular and metabolic protection of supplementation of GS variety after storage in classic cold (GSCC) and extreme ultra-low oxygen conditions (GSXO) in the apolipoprotein E-deficient 8-week-old mice fed with high fat diet for 14 weeks.

Circulating microparticles released during dyslipidemia may exert deleterious effects on blood vessels and endothelial function.

Aims: To compare the bioactivity of circulating microparticles (MPs) isolated from dyslipidemic Psammomys obesus (P. obesus) fed a high-energy diet (HED) with those released from healthy P. obesus fed a normal diet (ND).

Extracellular Vesicles: New Bullets to Fight Fungal Infections.

While behaving as a commensal yeast in healthy people, Candida albicans remains the deadliest fungal pathogen in immunocompromised patients. Halder et al. deciphered unprecedented immunomodulatory properties of monocyte extracellular vesicles in response to Candida infections, paving the way to consider therapeutic innovations for fungal infections but also inflammatory diseases.

Large Extracellular Vesicle-Associated Rap1 Accumulates in Atherosclerotic Plaques, Correlates With Vascular Risks and Is Involved in Atherosclerosis.

Rationale: Metabolic syndrome (MetS) is a cluster of interrelated risk factors for cardiovascular diseases and atherosclerosis. Circulating levels of large extracellular vesicles (lEVs), submicrometer-sized vesicles released from plasma membrane, from MetS patients were shown to induce endothelial dysfunction, but their role in early stage of atherosclerosis and on vascular smooth muscle cells (SMC) remain to be fully elucidated.

Objective: To determine the mechanisms by which lEVs lead to the progression of atherosclerosis in the setting of MetS.

Sleep apnoea and endothelial dysfunction: An individual patient data meta-analysis.

We performed an individual patient data meta-analysis to investigate the association between obstructive sleep apnoea (OSA) severity and the reactive hyperaemia index (RHI) measured by peripheral arterial tonometry (PAT), a validated measurement of endothelial function, and a strong predictor of late cardiovascular (CV) events. Patients from 12 studies underwent PAT and overnight polysomnography or respiratory polygraphy for suspected OSA. Endothelial dysfunction was defined by a log-transformed RHI<0.

Carrot Genotypes Contrasted by Root Color and Grown under Different Conditions Displayed Differential Pharmacological Profiles in Vascular and Metabolic Cells.

Carrots' genotype and growing conditions influence their potential properties to fight against cardiovascular and metabolic diseases. The present study evaluated the influence of carrot genotypes contrasted by root color (Bolero, Presto, Karotan, Deep Purple, Kintoki and Blanche des Vosges) growing under standard, water-restricted, biotic stress ( inoculation), and combined stress conditions (water restriction and inoculation). The effect of carrots' polyphenol and carotenoid content was assessed on endothelial and smooth muscle cells, hepatocytes, adipocytes and macrophages functions (oxidative stress, apoptosis, proliferation, lipid accumulation and inflammation).