Proponents for electronic cigarettes (E-cigs) claim that they are a safe alternative to tobacco-based cigarettes; however, little is known about the long-term effects of exposure E-cig vapor on vascular function. The purpose this study was determine cardiovascular consequences chronic exposure. Female mice (C57BL/6 background strain) were randomly assigned daily vapor, standard (3R4F reference) cigarette smoke, or filtered air ( n = 15/group). Respective whole body exposures consisted four...

Cigarette smoke (CS) is the most common risk factor for chronic obstructive pulmonary disease (COPD). The present study aimed to elucidate whether mtDNA released upon CS exposure and detected in plasma of former smokers affected by COPD as a possible consequence airway damage. We measured cell-free (cf-mtDNA) nuclear DNA (cf-nDNA) patient mouse serum with CS-induced emphysema. patients mice emphysema showed increased cf-mtDNA levels. In cell culture, sublethal dose CSE decreased...

Pulmonary arterial hypertension (PAH) is a complex degenerative disorder marked by aberrant vascular remodeling associated with hyperproliferation and migration of endothelial cells (ECs). Previous reports implicated bone morphogenetic protein antagonist Gremlin 1 in this process; however, little known the molecular mechanisms involved. The current study was designed to test whether redox signaling initiated NADPH oxidase (Nox1) could promote transcription factor CREB activation (Ref-1),...

Pulmonary hypertension (PH) is a leading cause of death in sickle cell disease (SCD) patients. Hemolysis and oxidative stress contribute to SCD-associated PH. We have reported that the protein thrombospondin-1 (TSP1) elevated plasma patients with SCD and, by interacting its receptor CD47, limits vasodilation distal pulmonary arteries ex vivo. hypothesized TSP1-CD47 interaction may promote PH SCD. found TSP1 CD47 are upregulated lungs Berkeley (BERK) sickling (Sickle) mice then generated...

The metabolic syndrome (MetS) is highly prevalent in the North American population and associated with increased risk for development of cerebrovascular disease. This study determined structural functional changes middle cerebral arteries (MCA) during progression MetS effects chronic pharmacological interventions on mitigating vascular alterations obese Zucker rats (OZR), a translationally relevant model MetS. reactivity wall mechanics ex vivo pressurized MCA from lean (LZR) OZR were at 7-8,...

First described as essential to the phagocytic activity of leukocytes, Nox2-derived ROS have emerged mediators a range cellular and tissue responses across species from salubrious deleterious consequences. Knowledge their role in inflammation is limited, however. We postulated that TNFα-induced endothelial reactive oxygen (ROS) generation pro-inflammatory signaling would be ameliorated by targeting Nox2. Herein, we silico-modelled two first-in-class Nox2 inhibitors developed our laboratory,...

In an aging population, intense interest has shifted toward prolonging health span. Mounting evidence suggests that cellular reactive species are propagators of cell damage, inflammation, and senescence. Thus, such have emerged as putative provocateurs targets for senolysis, a clearer understanding their molecular origin regulation is paramount importance. inquiry into signaling triggered by proxy instigator, hyperglycemia, we show NADPH Oxidase (NOX) drives DNA damage alters nuclear...

Evolution of metabolic syndrome is associated with a progressive reduction in skeletal muscle microvessel density, known as rarefaction. Although contributing to impairments mass transport and exchange, the temporal development rarefaction mechanisms that lead loss are both unclear critical areas for investigation. previous work suggests severity obese Zucker rats (OZR) predicted by chronic vascular nitric oxide (NO) bioavailability, we have determined this hides biphasic rarefaction, early...

New Findings What is the central question of this study? Tumour necrosis factor‐α (TNFα) has been shown to impair vascular function, but impact thoracic aorta perivascular adipose tissue (tPVAT)‐derived TNFα on tPVAT and aortic function in metabolic syndrome unknown. main finding its importance? Release by causes production reactive oxygen species through activation an NADPH‐oxidase 2 (NOX2)‐dependent pathway, activates mediates stiffness, potentially matrix metalloproteinase 9 activity....

The aim of the study was to determine effects exercise training on improving thoracic perivascular adipose tissue (tPVAT) phenotype (inflammation, oxidative stress, and proteasome function) in metabolic syndrome its subsequent actions aortic function. Lean obese (model syndrome) Zucker rats (n=8/group) underwent 8-weeks control conditions or treadmill (70% max speed, 1 h/day, 5 days/week). At end intervention, tPVAT removed conditioned media made. cleaned aorta attached a force transducer...

What is the central question of this study? How does chronic stress impact cerebrovascular function and metabolic syndrome accelerate adaptations to stress? role exercise training have in preventing changes syndrome? main finding its importance? Stressful conditions lead pathological cerebrovasculature via an oxidative nitric oxide pathway, presence produces a greater susceptibility stress-induced dysfunction. The results also provide insight into mechanisms that may contribute influence...

Abstract Background Pregnancy is associated with many rapid biological adaptations that support healthy development of the growing fetus. One which critical to fetal health and coordination between maternal liver derived substrates vascular delivery. This crucial adaptation can be potentially derailed by inhalation toxicants. Engineered nanomaterials (ENM) are commonly used in household industrial products as well medicinal applications. As such, potential risk exposure remains a concern,...

Pulmonary arterial hypertension (PAH) is a rare yet devastating and incurable disease with few treatment options. The underlying mechanisms of PAH appear to involve substantial cellular proliferation vascular remodeling, causing right ventricular overload eventual heart failure. Recent evidence suggests significant seminal role the pulmonary endothelium in initiation promotion PAH. Our previous work identified elevated reactive oxygen species (ROS)-producing enzyme NADPH oxidase 1 (NOX1)...

Xanthine oxidase (XO) catalyzes the catabolism of hypoxanthine to xanthine and uric acid, generating oxidants as a byproduct. Importantly, XO activity is elevated in numerous hemolytic conditions including sickle cell disease (SCD); however, role this context has not been elucidated. Whereas long-standing dogma suggests levels vascular compartment contribute pathology via increased oxidant production, herein, we demonstrate, for first time, that an unexpected protective during hemolysis....

Acute and chronic stress have been reported to differing effects on physical activity in rodents, but no study has examined a protocol that incorporates stressors often experienced by rodents throughout day. To examine this, the of Unpredictable Chronic Mild Stress (UCMS) voluntary running wheel at multiple time points, and/or response acute removal was determined. Twenty male Balb/c mice were given access accustomed wheels for 4 weeks, after which they randomized into 2 groups; exercise...

New Findings What is the central question of this study? Thoracic perivascular adipose tissue (tPVAT) known to, in part, regulate aortic function: what are effects unpredictable chronic mild stress (UCMS) on tPVAT regulation function and role exercise training alleviating potential negative actions UCMS tPVAT? main finding its importance? causes to disrupt endothelium‐dependent dilatation, increases inflammatory cytokine production diminishes tPVAT‐adiponectin. Exercise proved efficacious...

We recently reported a previously unknown salutary role for xanthine oxidoreductase (XOR) in intravascular heme overload whereby hepatocellular export of XOR to the circulation was identified as seminal step affording protection. However, cellular signaling and mechanisms underpinning this process were not identified. Here, we present novel data showing hepatocytes upregulate expression/protein abundance actively release it extracellular compartment following exposure hemopexin-bound hemin,...

Xanthine oxidase (XO) mediates vascular function. Chronic stress impairs cerebrovascular function and increases the risk of stroke cognitive decline. Our study determined role XO on stress-induced dysfunction We measured middle cerebral artery (MCA) function, free radical formation, working memory in 6-month-old C57BL/6 mice who underwent 8 weeks control conditions or unpredictable chronic mild (UCMS) with without febuxostat (50 mg/L), a inhibitor. UCMS had an impaired MCA dilation to...

The present study examined the effect of unpredictable chronic mild stress (UCMS) on peripheral microvessel function in healthy and metabolic syndrome (MetS) rodents whether exercise training could prevent vascular dysfunction associated with UCMS.Lean obese (model MetS) Zucker rats (LZR OZR) were exposed to 8 wk UCMS, (Ex), UCMS + Ex, or control conditions. At end intervention, gracilis arterioles (GA) isolated hung a pressurized myobath assess endothelium-dependent (EDD)...

The metabolic syndrome (MetS) is associated with threefold increased risk of cardiovascular (CV) morbidity and mortality, which partly due to a blunted CV reserve capacity, reflected by reduced peak exercise left ventricular (LV) contractility aerobic capacity arterial-ventricular coupling. To date, no study has examined whether training in MetS can reverse dysfunction. Furthermore, examining how alters function group individuals before the development diabetes and/or overt disease provide...

Arterial stiffening (AS) is characterized by the loss of elasticity arteries and an independent risk factor for cardiovascular (CV) mortality.We tested hypothesis that shallow water aerobics can lower AS in older individuals with CV factors.Participants were randomized into two groups.The Con group remained inactive, whereas ExT exercised 10 weeks.Carotid-tofemoral pulse wave velocity was used to measure analysis determine central blood pressures pre-and postintervention.A significant time...

New Findings What is the central question of this study? Does a stroke event influence aortic endothelial function; and what role peripheral circulating leucocytes in on vascular reactivity aorta? main finding its importance? In vitro co‐culture experiments demonstrated that endothelium‐dependent relaxation was impaired when rat rings were co‐cultured with stimulated serum from patients. Impaired not observed without patients or age‐matched control leucocytes. These data suggest...