Guidelines for Assessing Maternal Cardiovascular Physiology During Pregnancy and Postpartum.

Maternal mortality rates are at an all-time high across the world and are set to increase in subsequent years. Cardiovascular disease is the leading cause of death during pregnancy and postpartum, especially in the US. Therefore, understanding the physiological changes in the cardiovascular system during normal pregnancy is necessary to understand disease-related pathology. Significant systemic and cardiovascular physiological changes occur during pregnancy that are essential for supporting the maternal-fetal dyad. The physiological impact of pregnancy on the cardiovascular system has been examined in both experimental animal models and in humans. However, there is a continued need in this field of study to provide increased rigor and reproducibility. Therefore, these guidelines aim to provide information regarding best practices and recommendations to accurately and rigorously measure cardiovascular physiology during normal and cardiovascular-disease-complicated pregnancies in human and animal models.

The normal distribution of the hypoxic ventilatory response and methodological impacts: a meta-analysis and computational investigation.

The hypoxic ventilatory response (HVR) is the increase in breathing in response to reduced arterial oxygen pressure. Over several decades, studies have revealed substantial population-level differences in the magnitude of the HVR as well as significant inter-individual variation. In particular, low HVRs occur frequently in Andean high-altitude native populations. However, our group conducted hundreds of HVR measures over several years and commonly observed low responses in sea-level populations as well. As a result, we aimed to determine the normal HVR distribution, whether low responses were common, and to what extent variation in study protocols influence these findings. We conducted a comprehensive search of the literature and examined the distributions of HVR values across 78 studies that utilized step-down/steady-state or progressive hypoxia methods in untreated, healthy human subjects. Several studies included multiple datasets across different populations or experimental conditions. In the final analysis, 72 datasets reported mean HVR values and 60 datasets provided raw HVR datasets. Of the 60 datasets reporting raw HVR values, 35 (58.3%) were at least moderately positively skewed (skew > 0.5), and 21 (35%) were significantly positively skewed (skew > 1), indicating that lower HVR values are common. The skewness of HVR distributions does not appear to be an artifact of methodology or the unit with which the HVR is reported. Further analysis demonstrated that the use of step-down hypoxia versus progressive hypoxia methods did not have a significant impact on average HVR values, but that isocapnic protocols produced higher HVRs than poikilocapnic protocols. This work provides a reference for expected HVR values and illustrates substantial inter-individual variation in this key reflex. Finally, the prevalence of low HVRs in the general population provides insight into our understanding of blunted HVRs in high-altitude adapted groups. KEY POINTS: The hypoxic ventilatory response (HVR) plays a crucial role in determining an individual's predisposition to hypoxia-related pathologies. There is notable variability in HVR sensitivity across individuals as well as significant population-level differences. We report that the normal distribution of the HVR is positively skewed, with a significant prevalence of low HVR values amongst the general healthy population. We also find no significant impact of the experimental protocol used to induce hypoxia, although HVR is greater with isocapnic versus poikilocapnic methods. These results provide insight into the normal distribution of the HVR, which could be useful in clinical decisions of diseases related to hypoxaemia. Additionally, the low HVR values found within the general population provide insight into the genetic adaptations found in populations residing in high altitudes.

Effects of electronic cigarette E-liquid and device wattage on vascular function.

Electronic cigarettes (e-cigs) are customizable tobacco products that allow users to select e-liquid composition, flavors, and (in some devices) adjust wattage or heat used to generate e-cig aerosol. This study compared vascular outcomes in a conducting vessel (thoracic aorta) and a resistance artery (middle cerebral artery, MCA) in C57Bl/6 mice exposed to e-cig aerosol generated from either pure vegetable glycerin (VG) or pure propylene glycol (PG) over 60-min (Study 1), and separately the effect of using 5- vs. 30-watt settings with an exposure of 100-min (Study 2). In Study 1, aortic endothelial-dependent-dilation (EDD) was only impaired with PG- exposure (p < 0.05) compared with air. In the MCA, EDD response was impaired by ∼50% in both VG and PG groups compared with air (p < 0.05). In Study 2, the aortic EDD responses were not different for either 5- or 30-watt exposed groups compared with air controls; however, in the MCA, both 5- and 30-watt groups were impaired by 32% and 55%, respectively, compared with air controls (p < 0.05). These pre-clinical data provide evidence that chronic exposure to aerosol produced by either VG or PG, and regardless of the wattage used, leads to vascular dysfunction at multiple levels within the arterial system. For all exposures, we observed greater impairment of arterial reactivity in a resistance artery (i.e. MCA) compared with the aorta. These data could suggest the smaller arteries may be more sensitive or first to be affected, or that different mechanism(s) for impairment may be involved depending on arterial hierarchy.

Nicotine and Microvascular Responses in Skeletal Muscle from Acute Exposure to Cigarettes and Vaping.

Despite claims of safety or harm reduction for electronic cigarettes (E-cig) use (also known as vaping), emerging evidence indicates that E-cigs are not likely safe, or necessarily safer than traditional cigarettes, when considering the user's risk of developing vascular dysfunction/disease. E-cigs are different from regular cigarettes in that E-cig devices are highly customizable, and users can change the e-liquid composition (such as the base solution, flavors, and nicotine level). Since the effects of E-cigs on the microvascular responses in skeletal muscle are poorly understood, we used intravital microscopy with an acute (one-time 10 puff) exposure paradigm to evaluate the individual components of e-liquid on vascular tone and endothelial function in the arterioles of the gluteus maximus muscle of anesthetized C57Bl/6 mice. Consistent with the molecular responses seen with endothelial cells, we found that the peripheral vasoconstriction response was similar between mice exposed to E-cig aerosol or cigarette smoke (i.e., 3R4F reference cigarette); this response was not nicotine dependent, and endothelial cell-mediated vasodilation was not altered within this acute exposure paradigm. We also report that, regardless of the base solution component [i.e., vegetable glycerin (VG)-only or propylene glycol (PG)-only], the vasoconstriction responses were the same in mice with inhalation exposure to 3R4F cigarette smoke or E-cig aerosol. Key findings from this work reveal that some component other than nicotine, in inhaled smoke or aerosol, is responsible for triggering peripheral vasoconstriction in skeletal muscle, and that regardless of one's preference for an E-cig base solution composition (i.e., ratio of VG-to-PG), the acute physiological response to blood vessels appears to be the same. The data suggest that vaping is not likely to be 'safer' than smoking towards blood vessels and can be expected to produce and/or result in the same adverse vascular health outcomes associated with smoking cigarettes.

Short-term exposure of female BALB/cJ mice to e-cigarette aerosol promotes neutrophil recruitment and enhances neutrophil-platelet aggregation in pulmonary microvasculature.

Despite the perception that e-cigarettes are safer than conventional cigarettes, numerous findings demonstrated that e-cigarette aerosol (EC) exposure induced compromised immune functionality, vascular changes even after acute exposure, and lung injury. Notably, altered neutrophil functionality and platelet hemodynamics have been observed post-EC exposure. It was hypothesized that EC exposure initiates an inflammatory response resulting in altered neutrophil behavior and increased neutrophil-platelet interaction in the pulmonary microvasculature. Neutrophil and platelet responses were examined up to 48 hrs following whole-body, short-term EC exposure without flavorants or nicotine in a murine model, which most closely modeled secondhand exposure. This study is the first to investigate the impact of EC exposure through lung intravital imaging. Compared to room air-exposed mice, EC-exposed mice displayed significantly increased 1.7‒1.9-fold number of neutrophils in the pulmonary microvasculature associated with no marked change in neutrophils within whole blood or bronchoalveolar lavage fluid (BALF). Neutrophil-platelet interactions were also significantly elevated 1.9‒2.5-fold in exposed mice. Plasma concentration of myeloperoxidase was markedly reduced 1.5-fold 48 hr following exposure cessation, suggesting suppressed neutrophil antimicrobial activity. Cytokine expression exhibited changes indicating vascular damage. Effects persisted for 48 hr post-EC exposure. Data demonstrated that EC exposure repeated for 3 consecutive days in 2.5 hr intervals in the absence of flavorants or nicotine resulted in modified pulmonary vasculature hemodynamics, altered immune functionality, and a pro-inflammatory state in female BALB/cJ mice.

Maternal electronic cigarette use during pregnancy affects long-term arterial function in offspring.

Vaping, or electronic cigarette (ecig) use, is prevalent among pregnant women, although little is known about the effects of perinatal ecig use on cardiovascular health of the progeny (even when using nicotine-free e-liquid). Maternal toxicant inhalation may adversely affect vital conduit vessel development. We tested the hypothesis that perinatal exposure to maternal vaping would lead to a dose-dependent dysfunction that would persist into later life of offspring. Pregnant Sprague-Dawley rats were exposed to either nicotine-free (ecig0) or nicotine-containing ecig aerosol (18 mg/mL, ecig18) starting on gestational day 2 and continued until pups were weaned (postnatal day 21). Pups were never directly exposed. Conduit artery function (stiffness and reactivity) and structure were assessed in 3- and 7-mo-old offspring. At 3 mo, pulse wave velocity (PWV) in the ecig0 and ecig18 offspring was significantly higher than controls in both the 20 puffs/day (6.6 ± 2.1 and 4.8 ± 1.3 vs. 3.2 ± 0.7 m/s, respectively, P < 0.05, means ± SD) and in 60 puffs/day exposure cohort (7.5 ± 2.8 and 7.5 ± 2.5 vs. 3.2 ± 0.5 m/s, respectively, P < 0.01). Wire myography revealed (range of 23%-31%) impaired aortic relaxation in all ecig exposure groups (with or without nicotine). Incubation of vessels with TEMPOL or Febuxostat reversed the aortic dysfunction, implicating the involvement of reactive oxygen species. Nearly identical changes and pattern was seen in vascular outcomes of 7-mo-old offspring. The take-home message from this preclinical study is that maternal vaping during pregnancy, with or without nicotine, leads to maladaptations in vascular (aortic) development that persist into adult life of offspring.NEW & NOTEWORTHY We observe a significant alteration in arterial structure and function in adolescent and adult offspring due to developmental exposure to toxicants resulting from perinatal maternal vaping. Taken together with previous work that described lasting dysfunction in cerebral microvasculature in offspring, these data underscore the adverse consequences of maternal exposure to electronic cigarette aerosol in conduit and resistance vessels alike, irrespective of nicotine content.

The development of peripheral microvasculopathy with chronic metabolic disease in obese Zucker rats: a retrograde emergence?

The study of peripheral vasculopathy with chronic metabolic disease is challenged by divergent contributions from spatial (the level of resolution or specific tissue being studied) and temporal origins (evolution of the developing impairments in time). Over many years of studying the development of skeletal muscle vasculopathy and its functional implications, we may be at the point of presenting an integrated conceptual model that addresses these challenges within the obese Zucker rat (OZR) model. At the early stages of metabolic disease, where systemic markers of elevated cardiovascular disease risk are present, the only evidence of vascular dysfunction is at postcapillary and collecting venules, where leukocyte adhesion/rolling is elevated with impaired venular endothelial function. As metabolic disease severity and duration increases, reduced microvessel density becomes evident as well as increased variability in microvascular hematocrit. Subsequently, hemodynamic impairments to distal arteriolar networks emerge, manifesting as increasing perfusion heterogeneity and impaired arteriolar reactivity. This retrograde "wave of dysfunction" continues, creating a condition wherein deficiencies to the distal arteriolar, capillary, and venular microcirculation stabilize and impairments to proximal arteriolar reactivity, wall mechanics, and perfusion distribution evolve. This proximal arteriolar dysfunction parallels increasing failure in fatigue resistance, hyperemic responses, and O2 uptake within self-perfused skeletal muscle. Taken together, these results present a conceptual model for the retrograde development of peripheral vasculopathy with chronic metabolic disease and provide insight into the timing and targeting of interventional strategies to improve health outcomes.NEW & NOTEWORTHY Working from an established database spanning multiple scales and times, we studied progression of peripheral microvascular dysfunction in chronic metabolic disease. The data implicate the postcapillary venular endothelium as the initiating site for vasculopathy. Indicators of dysfunction, spanning network structures, hemodynamics, vascular reactivity, and perfusion progress in an insidious retrograde manner to present as functional impairments to muscle blood flow and performance much later. The silent vasculopathy progression may provide insight into clinical treatment challenges.

Short-term effects of electronic cigarettes on cerebrovascular function: A time course study.

NEW FINDINGS: What is the central question of this study? Acute exposure to electronic cigarettes (Ecigs) triggers abnormal vascular responses in systemic arteries; however, effects on cerebral vessels are poorly understood and time for recovery is not known. We hypothesized that exposure to cigarettes or Ecigs would trigger rapid (<4 h) impairment of the middle cerebral artery (MCA) but that this would resolve by 24 h. What is the main finding and its importance? Cigarettes and Ecigs caused similar degree and duration of MCA impairment. We find it takes ~72 hours after exposure for MCA function to return to normal. This suggests that Ecig use is likely to produce similar adverse vascular health outcomes to those seen with cigarette smoke. ABSTRACT: Temporal influences of electronic cigarettes (Ecigs) on blood vessels are poorly understood. In this study, we evaluated a single episode of cigarette versus Ecig exposure on middle cerebral artery (MCA) reactivity and determined how long after the exposure MCA responses took to return to normal. We hypothesized that cigarette and Ecig exposure would induce rapid (<4 h) reduction in MCA endothelial function and would resolve within 24 h. Sprague-Dawley rats (4 months old) were exposed to either air (n = 5), traditional cigarettes (20 puffs, n = 16) or Ecigs (20-puff group, n = 16; or 60-puff group, n = 12). Thereafter, the cigarette and Ecig groups were randomly assigned for postexposure vessel myography testing on day 0 (D0, 1-4 h postexposure), day 1 (D1, 24-28 h postexposure), day 2 (D2, 48-52 h postexposure) and day 3 (72-76 h postexposure). The greatest effect on endothelium-dependent dilatation was observed within 24 h of exposure (∼50% decline between D0 and D1) for both cigarette and Ecig groups, and impairment persisted with all groups for up to 3 days. Changes in endothelium-independent dilatation responses were less severe (∼27%) and shorter lived (recovering by D2) compared with endothelium-dependent dilatation responses. Vasoconstriction in response to serotonin (5-HT) was similar to endothelium-independent dilatation, with greatest impairment (∼45% for all exposure groups) at D0-D1, returning to normal by D2. These data show that exposure to cigarettes and Ecigs triggers a similar level/duration of cerebrovascular dysfunction after a single exposure. The finding that Ecig (without nicotine) and cigarette (with nicotine) exposure produce the same effects suggesting that nicotine is not likely to be triggering MCA dysfunction, and that vaping (with/without nicotine) has potential to produce the same vascular harm and/or disease as smoking.

Sex differences in skeletal muscle revealed through fiber type, capillarity, and transcriptomics profiling in mice.

Skeletal muscle anatomy and physiology are sexually dimorphic but molecular underpinnings and muscle-specificity are not well-established. Variances in metabolic health, fitness level, sedentary behavior, genetics, and age make it difficult to discern inherent sex effects in humans. Therefore, mice under well-controlled conditions were used to determine female and male (n = 19/sex) skeletal muscle fiber type/size and capillarity in superficial and deep gastrocnemius (GA-s, GA-d), soleus (SOL), extensor digitorum longus (EDL), and plantaris (PLT), and transcriptome patterns were also determined (GA, SOL). Summed muscle weight strongly correlated with lean body mass (r2  = 0.67, p < 0.0001, both sexes). Other phenotypes were muscle-specific: e.g., capillarity (higher density, male GA-s), myofiber size (higher, male EDL), and fiber type (higher, lower type I and type II prevalences, respectively, in female SOL). There were broad differences in transcriptomics, with >6000 (GA) and >4000 (SOL) mRNAs differentially-expressed by sex; only a minority of these were shared across GA and SOL. Pathway analyses revealed differences in ribosome biology, transcription, and RNA processing. Curation of sexually dimorphic muscle transcripts shared in GA and SOL, and literature datasets from mice and humans, identified 11 genes that we propose are canonical to innate sex differences in muscle: Xist, Kdm6a, Grb10, Oas2, Rps4x (higher, females) and Ddx3y, Kdm5d, Irx3, Wwp1, Aldh1a1, Cd24a (higher, males). These genes and those with the highest "sex-biased" expression in our study do not contain estrogen-response elements (exception, Greb1), but a subset are proposed to be regulated through androgen response elements. We hypothesize that innate muscle sexual dimorphism in mice and humans is triggered and then maintained by classic X inactivation (Xist, females) and Y activation (Ddx3y, males), with coincident engagement of X encoded (Kdm6a) and Y encoded (Kdm5d) demethylase epigenetic regulators that are complemented by modulation at some regions of the genome that respond to androgen.

Metabolic physiology and skeletal muscle phenotypes in male and female myoglobin knockout mice.

Myoglobin (Mb) is a regulator of O2 bioavailability in type I muscle and heart, at least when tissue O2 levels drop. Mb also plays a role in regulating cellular nitric oxide (NO) pools. Robust binding of long-chain fatty acids and long-chain acylcarnitines to Mb, and enhanced glucose metabolism in hearts of Mb knockout (KO) mice, suggest additional roles in muscle intermediary metabolism and fuel selection. To evaluate this hypothesis, we measured energy expenditure (EE), respiratory exchange ratio (RER), body weight gain and adiposity, glucose tolerance, and insulin sensitivity in Mb knockout (Mb-/-) and wild-type (WT) mice challenged with a high-fat diet (HFD, 45% of calories). In males (n = 10/genotype) and females (n = 9/genotype) tested at 5-6, 11-12, and 17-18 wk, there were no genotype effects on RER, EE, or food intake. RER and EE during cold (10°C, 72 h), and glucose and insulin tolerance, were not different compared with within-sex WT controls. At ∼18 and ∼19 wk of age, female Mb-/- adiposity was ∼42%-48% higher versus WT females (P = 0.1). Transcriptomics analyses (whole gastrocnemius, soleus) revealed few consistent changes, with the notable exception of a 20% drop in soleus transferrin receptor (Tfrc) mRNA. Capillarity indices were significantly increased in Mb-/-, specifically in Mb-rich soleus and deep gastrocnemius. The results indicate that Mb loss does not have a major impact on whole body glucose homeostasis, EE, RER, or response to a cold challenge in mice. However, the greater adiposity in female Mb-/- mice indicates a sex-specific effect of Mb KO on fat storage and feed efficiency.NEW & NOTEWORTHY The roles of myoglobin remain to be elaborated. We address sexual dimorphism in terms of outcomes in response to the loss of myoglobin in knockout mice and perform, for the first time, a series of comprehensive metabolic studies under conditions in which fat is mobilized (high-fat diet, cold). The results highlight that myoglobin is not necessary and sufficient for maintaining oxidative metabolism and point to alternative roles for this protein in muscle and heart.

Psychosocial Factors Associated with E-Cigarette Use among Young Adults in a 4-Year University in Appalachia.

OBJECTIVES: In order to determine methods to reduce vaping prevalence, motivations for use and co-occurring health behaviors and disorders need to be determined. This study investigated vaping characteristics and associated health behaviors in a young adult Appalachian college population. METHODS: Students attending an Appalachian university were invited to participate in an online survey measuring their use of e-cigarettes, motivations for use, mental health, and Adverse Childhood Experiences (ACEs). Analysis included prevalence of e-cigarette use and associations between e-cigarette use and Appalachian identity, mental health, and ACEs. RESULTS: Participants (N = 3398) stated that the most common motivator for using e-cigarettes was to decrease stress, followed by the good taste, friends' usage, and wanting to quit cigarettes. E-cigarette use was associated with alcohol use, anxiety, depression, stress, and Adverse Childhood Experiences (ACEs) and these variables were placed into a full logistic regression model, in which anxiety and stress were no longer significant, and alcohol use was the strongest association (OR 1.36 95% CI 1.35-1.42, p<.0001).Conclusions/importance: Findings demonstrate a need for efforts to reduce e-cigarette use to focus on the co-use of alcohol, co-occurring mental health disorders, and the social and enjoyment motivations for use.

Chronic stress induced perivascular adipose tissue impairment of aortic function and the therapeutic effect of exercise.

NEW FINDINGS: What is the central question of this study? Thoracic perivascular adipose tissue (tPVAT) is known to, in part, regulate aortic function: what are the effects of unpredictable chronic mild stress (UCMS) on the tPVAT regulation of aortic function and what is the role of exercise training in alleviating the potential negative actions of UCMS on tPVAT? What is the main finding and its importance? UCMS causes tPVAT to disrupt endothelium-dependent dilatation, increases inflammatory cytokine production and diminishes tPVAT-adiponectin. Exercise training proved efficacious in preventing tPVAT-mediated disruption of aortic function. The data support a tPVAT mechanism through which chronic stress negatively impacts vascular health, which adds to our knowledge of how psychological disorders might increase the risk of cardiovascular disease. ABSTRACT: Chronic stress is a major risk for cardiovascular disease. Perivascular adipose tissue (PVAT) has been shown to regulate vascular function; however, the impact of chronic stress and the comorbidity of metabolic syndrome (MetS) on thoracic (t)PVAT is unknown. Additionally, aerobic exercise training (AET) is known to combat the pathology of MetS and chronic stress, but the role of tPVAT in these actions is also unknown. Therefore, the purpose of this study was to examine the effects of unpredictable chronic mild stress (UCMS) on the tPVAT regulation of aortic function and the preventative effect of AET. Lean (LZR) and obese (OZR) Zucker rats (16-17 weeks old) were exposed to 8 weeks of UCMS with and without treadmill exercise (AET). In LZR, UCMS impaired aortic endothelium-dependent dilatation (EDD) (assessed ex vivo by wire myography) and aortic stiffness (assessed by elastic modulus) with no change in OZR subject to UCMS. However, both LZR and OZR UCMS tPVAT impaired EDD compared to respective controls. LZR and OZR subject to UCMS had higher oxidative stress production, diminished adiponectin and impaired aortic nitric oxide levels. Divergently, UCMS induced greater inflammatory cytokine production in LZR UCMS tPVAT, but not in OZR UCMS tPVAT. AET prevented the tPVAT impairment of aortic relaxation with UCMS in LZR and OZR. Additionally, AET reduced aortic stiffness in both LZR and OZR. These beneficial effects on tPVAT regulation of the aorta are likely due to AET preservation of adiponectin, reduced oxidative stress and inflammation, and enhanced nitric oxide. UCMS impaired tPVAT-regulated aortic function in LZR, and augmented MetS-induced EDD in OZR. Conversely, AET in combination with UCMS largely preserved aortic function and the tPVAT environment, in both groups.

Role of Perivascular Adipose Tissue and Exercise on Arterial Function with Obesity.

Adipose tissue and arterial dysfunction are common in the obese state. Perivascular adipose tissue (PVAT) plays an important role in mediating arterial health, and with obesity, the PVAT dysfunction negatively affects arterial health. Exercise training exerts direct and beneficial effects on PVAT, providing an additional and novel pathway by which exercise can improve arterial health in diseased populations.

Electronic Cigarettes and Vaping-Associated Lung Injury (EVALI): A Rural Appalachian Experience.

Background: Electronic cigarette use has increased dramatically since their introduction in 2007. Respiratory complications, particularly lipoid pneumonia, have been reported as early as 2012. An outbreak of pulmonary injury in 2019 has been reported in patients using vaping products.Research Question: To describe a rural Appalachian tertiary center's experience of EVALI and to identify novel mechanisms of pulmonary injury patterns.Study Design and Methods: We present a consecutive case series of 17 patients admitted to our rural, academic, tertiary care institution with EVALI from August 2019 to March 2020. Demographics, baseline characteristics, co-morbidities, vaping behavior, and hospital course were recorded. Broncho-alveolar lavage specimens were assessed for lipid-laden macrophages and hemosiderin-laden macrophages with stains for Oil-Red-O (n = 15) and Prussian Blue (n = 14) respectively.The patient volunteered e-liquid materials (n = 6), and vapors were analyzed using a proton transfer reaction time-of-flight mass spectrometer (PTR-TOF-MS) to describe the chemical profile. Post-discharge interviews were conducted.Results: The most common CT finding was bilateral ground-glass opacities with a predilection for lower lung zones. The most frequent pulmonary injury pattern was lipoid pneumonia. The majority of EVALI patients were critically ill requiring ventilation or ECMO. The most severely ill patients were noted to be positive for iron stains in macrophages and showed higher volatile organic compound (VOC) levels in chemical analysis.Interpretation: Based on our experience, EVALI in rural Appalachia presented with relatively severe respiratory failure. Worse outcomes appear to be correlated to high levels of VOCs, iron deposition in lungs, and concomitant infection.

Chronic electronic cigarette use elicits molecular changes related to pulmonary pathogenesis.

The relative safety of chronic exposure to electronic cigarette (e-cig) aerosol remains unclear in terms of lung pathogenesis. Therefore, this study aims to evaluate gene/protein biomarkers, which are associated with cigarette-induced pulmonary injury in animals chronically exposed to nicotine containing e-cig aerosol. C57BL/6 J mice were randomly assigned to three exposure groups: e-cig, tobacco cigarette smoke, and filtered air. Lung tissues and/or paraffin embedded slides were used to evaluate gene and/or protein expressions of the CYP450 metabolism (CYP1A1, CYP2A5, and CYP3A11), oxidative stress (Nrf2, SOD1), epithelial-mesenchymal transition (E-cadherin and vimentin), lung pathogenesis (AhR), and survival/apoptotic pathways (p-AKT, BCL-XL, p53, p21, and CRM1). Expressions of E-cadherin and CRM1 were significantly decreased, while CYP1A1, AhR, SOD1 and BCL-XL were significantly upregulated in the e-cig group compared to the control (p < 0.05). Nuclear sub-cellular localization of p53, evaluated by immunohistochemistry staining, in bronchiolar tissues was higher in the e-cig group (25.3 ± 2.7%) as compared to controls (12.1 ± 1.8%) (p < 0.01). Although the biomarkers responses were not identical, in general, the responses had similar qualitative trends between the e-cig and cigarette groups. As these related molecular changes are involved in the pathogenesis of cigarette-induced lung injury, the possibility exists that e-cigs can produce a similar outcome. Although further investigation is warranted, e-cigs are unlikely to be considered as safe in terms of pulmonary health.

Exercise training prevents the perivascular adipose tissue-induced aortic dysfunction with metabolic syndrome.

The aim of the study was to determine the effects of exercise training on improving the thoracic perivascular adipose tissue (tPVAT) phenotype (inflammation, oxidative stress, and proteasome function) in metabolic syndrome and its subsequent actions on aortic function. METHODS: Lean and obese (model of metabolic syndrome) Zucker rats (n=8/group) underwent 8-weeks of control conditions or treadmill exercise (70% of max speed, 1 h/day, 5 days/week). At the end of the intervention, the tPVAT was removed and conditioned media was made. The cleaned aorta was attached to a force transducer to assess endothelium-dependent and independent dilation in the presence or absence of tPVAT-conditioned media. tPVAT gene expression, inflammatory /oxidative phenotype, and proteasome function were assessed. RESULTS: The main findings were that Ex induced: (1) a beige-like, anti-inflammatory tPVAT phenotype; (2) a greater abundance of •NO in tPVAT; (3) a reduction in tPVAT oxidant production; and (4) an improved tPVAT proteasome function. Regarding aortic function, endothelium-dependent dilation was greater in exercised lean and obese groups vs. controls (p < 0.05). Lean control tPVAT improved aortic relaxation, whereas obese control tPVAT decreased aortic relaxation. In contrast, the obese Ex-tPVAT increased aortic dilation, whereas the lean Ex-tPVAT did not affect aortic dilation. CONCLUSION: Overall, exercise had the most dramatic impact on the obese tPVAT reflecting a change towards an environment with less oxidant load, less inflammation and improved proteasome function. Such beneficial changes to the tPVAT micro-environment with exercise likely played a significant role in mediating the improvement in aortic function in metabolic syndrome following 8 weeks of exercise.

Monetary Cost of the MyPlate Diet in Young Adults: Higher Expenses Associated with Increased Fruit and Vegetable Consumption.

BACKGROUND: Cost is a commonly reported barrier to healthy eating. This is a secondary research analysis designed to examine the food expenditures of young adults on a university campus following the United States Department of Agriculture (USDA) MyPlate guidelines for fruits and vegetables. METHODS: Meal receipts and dietary intake were recorded weekly. Anthropometrics and clinical assessments were recorded before intervention. Researchers rated compliance based on the participant's dietary food log, receipt matching, food pictures, and reports during weekly 1-hour consultations. RESULTS: Fifty-three young adults (18-30 years old) at-risk of, or diagnosed with, metabolic syndrome (MetS) were enrolled in the study, with 10 excluded (n = 43) from analyses due to enrollment in a fixed cost university campus dining meal plan. A two sample t-test assessed differences in food costs and regression analysis determined associations between food cost and diet compliance while controlling for confounding factors of age, sex, and body mass index (BMI). Diet compliant subjects (n = 38) had higher weekly food cost at $95.73 compared to noncompliant subjects (n = 5) who spent $66.24 (p=0.01). A regression analysis controlling for age, sex, BMI, and geographical region also indicated cost differences based on diet compliance (p < 0.0001). CONCLUSION: Results indicate an ∼$29.00 per week increase in food cost when eating the recommended amount of fruit and vegetables. These findings can contribute to research incentive design, program planning cost, and determining effective interventions to improve diet in this population.

Educational intervention improves fruit and vegetable intake in young adults with metabolic syndrome components.

The FRUVEDomics study investigates the effect of a diet intervention focused on increasing fruit and vegetable intake on the gut microbiome and cardiovascular health of young adults with/at risk for metabolic syndrome (MetS). It was hypothesized that the recommended diet would result in metabolic and gut microbiome changes. The 9-week dietary intervention adhered to the US Department of Agriculture Dietary Guidelines for Americans and focused on increasing fruit and vegetable intake to equal half of the diet. Seventeen eligible young adults with/or at high risk of MetS consented and completed preintervention and postintervention measurements, including anthropometric, body composition, cardiovascular, complete blood lipid panel, and collection of stool sample for microbial analysis. Participants attended weekly consultations to assess food logs, food receipts, and adherence to the diet. Following intention-to-treat guidelines, all 17 individuals were included in the dietary, clinical, and anthropometric analysis. Fruit and vegetable intake increased from 1.6 to 3.4 cups of fruits and vegetables (P < .001) daily. Total fiber (P = .02) and insoluble fiber (P < .0001) also increased. Clinical laboratory changes included an increase in sodium (P = .0006) and low-density lipoprotein cholesterol (P = .04). In the fecal microbiome, Erysipelotrichaceae (phylum Firmicutes) decreased (log2 fold change: -1.78, P = .01) and Caulobacteraceae (phylum Proteobacteria) increased (log2 fold change = 1.07, P = .01). Implementing a free-living 9-week diet, with intensive education and accountability, gave young adults at high risk for/or diagnosed with MetS the knowledge, skills, and feedback to improve diet. To yield greater impact, a longer diet intervention may be needed in this population.