The Effect of Cigarette Exposure on Intima-Media Thickness (IMT) and VCAM-1 Expression in the Aorta of Mus musculus Mice

The age period spanning late adolescence to emergent adulthood is associated with the highest prevalence of cigarette smoking in the United States, and is also a time of continued brain development. Nonetheless, although prior research has shown group differences in brain structure associated with smoking status in adults, few studies have examined how smoking and associated behavioral states relate to brain structure in this age group. Neuroimaging and lesion studies have suggested that the insula, a cortical region that integrates heterogeneous signals about internal states and contributes to executive functions, plays an important role in cigarette smoking behavior. Using high-resolution structural magnetic resonance imaging, we therefore measured cortical thickness of the insula in 18 smokers and 24 nonsmokers between the ages of 16 and 21 years. There were no group differences in insula thickness, but cigarette exposure (pack-years) was negatively associated with thickness in right insula. Cigarette dependence and the urge to smoke were negatively related to cortical thickness in the right ventral anterior insula. Although the results do not demonstrate causation, they do suggest that there are effects of cigarette exposure on brain structure in young smokers, with a relatively short smoking history. It is possible that changes in the brain due to prolonged exposure or to the progression of dependence lead to more extensive structural changes, manifested in the reported group differences between adult smokers and nonsmokers. Structural integrity of the insula may have implications for predicting long-term cigarette smoking and problems with other substance abuse in this population.

Passive smoking is the involuntary inhalation of cigarette smoke (CS) and has an adverse impact on oral health. We examined the effect of CS exposure on saliva and salivary glands (SGs). Cigarette smoke-exposed rats were intermittently housed in an animal chamber with whole-body exposure to CS until killed. Whole saliva was collected before CS exposure (0 day), and 15 and 30 days after the start of CS exposure. Saliva secretion was stimulated by administration of isoproterenol and pilocarpine after anesthesia. SGs were collected on 31 days. The increase in body weight of the CS-exposed rats was less than that of the control rats. Salivary flow rates did not differ at 0, 15 or 30 days after the start of CS exposure. However, the amylase and peroxidase activities and total protein content in the saliva were significantly lower in 15-day CS-exposed rats than in 15-day control rats. Histological examination of the SGs of CS-exposed rats showed vacuolar degeneration, vasodilation and hyperemia. These results suggest that CS exposure has adverse impacts on salivary composition and SGs, which could aggravate the oral environment.

Objectives: Antiphospholipid syndrome is characterised by increased thrombogenicity and/or pregnancy morbidity in the presence of raised levels of antiphospholipid antibodies (aPL). Increased oxidative properties of HDL (decreased activity of paraoxonase (PON) and accelerated atherosclerosis have been described in this syndrome. In this study, we assessed the functional properties of HDL and evaluated its impact on the vasculature in aPL positive patients and matched controls. Methods: We studied 77 women with positive aPL (APL) aged 46.6 ± 1.2 yrs (mean ± SE) and matched Controls of 77 women aged 47.5 ± 1.2 yrs. In all subjects, carotid intima media thickness (IMT), flow mediated dilatation (FMD) and pulse wave velocity (PWV) were measured. PON activity was assessed by measuring p-nitrophenol formation. HDL was isolated in APL (N = 6) and Controls (N = 6). The impact of HDL on human aortic endothelial cell (HAEC) nitric oxide (NO) and superoxide production were determined. Anti-inflammatory properties of HDL were examined by analyzing the effect of HDL on endothelial cell VCAM-1 expression and monocyte adhesion to activated HAEC. Results: APL had significantly increased IMT and PWV compared to Controls (0.75 ± 0.02mm vs 0.65 ± 0.01mm, p < 0.001 and 9.14 ± 0.18 m/s vs 8.56 ± 0.21m/s, p < 0.05 respectively) and decreased FMD (6.2 ± 0.5% vs 9.6 ± 0.5%, p < 0.001). PON activity was significantly reduced in APL compared to Controls (p = 0.006). PON activity was inversely associated with cIMT and PWV in APL (p < 0.05 for both) but not in Controls. HDL from Controls increased endothelial cell NO production, whereas in marked contrast HDL from APL reduced NO production by 20% (p < 0.0001). The beneficial effect of HDL on endothelial VCAM-1 expression, superoxide production and monocyte adhesion was diminished in APL (p < 0.05 for all). Conclusions: APL is associated with impaired vascular function and structure. PON activity is decreased in APL and is inversely associated with IMT and PWV. HDL in APL is associated with decreased endothelial NO production and has impaired anti-inflammatory and anti-oxidant properties. These findings suggest that HDL is dysfunctional in APL and support its role in promoting early vascular changes in antiphospholipid syndrome.

The novel strategy against ischemic stroke in metabolic syndrome (MetS) targeting at oxidative stress and inflammation has gained attention due to the limitation of the current therapy. Due to the antioxidant and anti-inflammation of the combined extract of Oryza sativa and Anethum graveolens, the cerebroprotective effect against cerebral ischemia in MetS condition has been focused. Since no data were available, this study was set up to determine the effects of the combined extract of Oryza sativa L. and Anethum graveolens Linn. against ischemic stroke in the animal model of metabolic syndrome. The possible underlying mechanism was also further investigated. Male Wistar rats (180-220 g) were fed with high-carbohydrate high-fat diet (HCHF diet) to induce metabolic syndrome-like condition. Then, MetS rats were subjected to reperfusion injury at the right middle cerebral artery. The combined extract of O. sativa and A. graveolens (OA extract) at doses of 0.5, 5, and 50 mg/kg BW was fed once daily for 21 days. Neurological assessment was performed every 7 days throughout the experimental period. At the end of study, brain infarction volume, neuron and glial fibrillary acidic protein- (GFAP-) positive cell density, the oxidative stress status, the expressions of proinflammatory cytokines (NF-κB, IL-6), and eNOS in the cortical area together with the expression of VCAM-1 and the histological changes of common carotid artery were determined. It was found that OA extract decreased brain infarction, neurological score, oxidative stress status, and inflammatory mediators but increased eNOS expression in the cortical area; the increased VCAM-1 and intima-media thickness together with the reduction of lumen diameter of common carotid artery of MetS eats with MCAO were also mitigated by OA extract. These data suggest the cerebroprotective effect of OA, and the underlying mechanism may occur partly via the improvement of oxidative stress status, inflammation, and brain blood supply.

Background Aorta and carotid intima-media thickness (IMT) is a measure of subclinical atherosclerosis and useful to assess cardiometabolic risk in the young. The in utero milieu may involve cardiometabolic programing and the development of cardiometabolic risk factors in children. Maternal smoking, alcohol consumption, and micronutrient deficiencies during pregnancy influence the development of the cardiovascular system through a process of DNA methylation. Aim To explore an association between maternal smoking and alcohol consumption during pregnancy and intima media thickness in 5-year-old children for a low-income setting. Methods Data were collected from 500 mother–child pairs at antenatal clinic visit, at birth, and at age 5 years. Anthropometric measurements were collected at birth and again at age 5 years. As well as clinical and ultrasound measurements at age 5 years. Clinical measurements, at age 5 years, included blood pressure, mean arterial pressure, and heart rate. Ultrasound measurements of the aorta and carotid arteries IMT were performed at age 5 years. Main outcome of interest was effect of dual teratogen exposure on the ultrasound measures IMT as indication of cardiometabolic risk. Results cIMT was significantly higher in children exposed to both alcohol and nicotine during pregnancy compared to those not exposed (p = .008). In separate linear models, dual in utero exposure (beta = 0.12; p = .01) and male sex (beta = 0.14; p = .01) were associated with higher right cIMT values (F(6,445) = 5.20; R 2 = 0.07, p < .01); male sex (beta = 0.13; p = .01) and low birth weight (beta = 0.07; p = .01) with higher left cIMT value (F(4,491) = 4.49; R 2 = 0.04; p = .01); and males sex (beta = 0.11; p = .02) with higher aorta IMT (F(6,459) = 5.63; R 2 = 0.07; p < .01). Significant positive correlations between maternal measures of adiposity, maternal MUAC (r = 0.10; p = .03), and maternal BMI (r = 0.12; p < .01) and right cIMT measurements adjusted for the BMI of the child at age 5 years as covariate. Blood pressure measurements at age 5 years were not significantly associated with IMT but, instead, correlated significantly and positively with the BMI of the child at age 5 years (p < .01). Conclusion Children exposed to both maternal smoking and alcohol consumption during pregnancy presented with cardiometabolic risk factors 5 years after birth. In addition, maternal adiposity, male sex, and low birth weight were associated with higher IMT at age 5 years.

Effects of Estrogen, Progesterone, and Combination Exposure on Interleukin-1β-Induced Expression of VCAM-1, ICAM-1, PECAM, and E-Selectin by Human Female Iliac Artery Endothelial Cells

Phosphatidylserine-containing liposomes: Therapeutic potentials against hypercholesterolemia and atherosclerosis

ObjectiveThe aim was to determine if endothelial VCAM-1 (eVCAM-1) expression in the common carotid artery (CCA) would correlate with predictive markers of atherosclerotic disease, would precede reduction of markers of endothelial cell function and would predict coronary artery disease (CAD).Methods and resultsCarotid arterial segments (bifurcation, proximal and distal CCA) were harvested from 14 and 24 month-old male castrated familial hypercholesterolemic (FH) swine, a model of spontaneous atherosclerosis. Quantification of local expression of eVCAM-1, intimal macrophage accumulation, oxidative stress, intima-media (I/M) ratio, intima-media thickness (IMT), endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (p-eNOS) in selected regions of the carotids revealed a relationship between local inflammation and atheroscle-rotic plaque progression. Importantly, inflammation was not uniform throughout the CCA. Endo-thelial VCAM-1 expression was the greatest at the bifurcation and increased with age. Finally, eV-CAM-1 best estimated the severity of CAD compared to blood levels of glucose, hypercholestero-lemia, carotid IMT, and p-eNOS.ConclusionOur data suggested that eVCAM-1 was closely associated with atherosclerotic plaque progression and preceded impairment of EDD. Thus, this study supported the use of carotid VCAM-1 targeting agents to estimate the severity of CAD.

Background: Air pollution is associated with cardiovascular morbidity and mortality; however, theunderlying mechanisms are not yet clearly understood. Several previous studies have implicated potentialmechanism action including oxidative stress, systemic inflammation, autonomic dysfunction, and endothelialdysfunction. Several epidemiological studies have examined the association between ICAM-1, VCAM-1and particulate matter.Objective: To describe the effect of soot particulate exposure in VCAM-1 expression in the mechanism ofcardiovascular dysfunctions.Method: The experiment was conducted in laboratory female rats (Rattus novergicus) and consisted of 3groups: Control group (n=10), without soot particulate exposure; Treatment 1 group (n=12), exposed bysoot particulate with the concentration of 532 mg/m3 an hour each day for 30 days; Treatment 2 group(n=12), exposed by soot particulate with the concentration of 1064 mg/m3 an hour each day for 30 days.Theexpression of VCAM-1 on cardiac tissue was measured after the end of treatment by immunohistochemicalexamination. The differentiation of VCAM-1 expression among the groups was tested using the Kruskal-Wallis test and the Mann-Whitney test.Results: The mean rank of VCAM-1 expression in the control group, treatment group 1 and treatment group2 was significantly different (8.85, 17.63, 24.58, p=0.001). There was a significant difference in VCAM-1expression by using the Mann-Whitney test among groups (p <0.05).Conclusion: The exposure to soot particles increased VCAM-1 expression significantly in laboratoryanimals. Our findings indicated the important role of the inflammatory activation pathway as a response tosoot particulate exposure in the mechanism of cardiovascular disease.

Background: Epidemiological evidence of the effects of long-term exposure to air pollution on the chronic processes of atherogenesis is limited.Objective: We investigated the association of long-term exposure to traffic-related air pollution with subclinical atherosclerosis, measured by carotid intima media thickness (IMT) and ankle–brachial index (ABI).Methods: We performed a cross-sectional analysis using data collected during the reexamination (2007–2010) of 2,780 participants in the REGICOR (Registre Gironí del Cor: the Gerona Heart Register) study, a population-based prospective cohort in Girona, Spain. Long-term exposure across residences was calculated as the last 10 years’ time-weighted average of residential nitrogen dioxide (NO2) estimates (based on a local-scale land-use regression model), traffic intensity in the nearest street, and traffic intensity in a 100 m buffer. Associations with IMT and ABI were estimated using linear regression and multinomial logistic regression, respectively, controlling for sex, age, smoking status, education, marital status, and several other potential confounders or intermediates.Results: Exposure contrasts between the 5th and 95th percentiles for NO2 (25 µg/m3), traffic intensity in the nearest street (15,000 vehicles/day), and traffic load within 100 m (7,200,000 vehicle-m/day) were associated with differences of 0.56% (95% CI: –1.5, 2.6%), 2.32% (95% CI: 0.48, 4.17%), and 1.91% (95% CI: –0.24, 4.06) percent difference in IMT, respectively. Exposures were positively associated with an ABI of > 1.3, but not an ABI of < 0.9. Stronger associations were observed among those with a high level of education and in men ≥ 60 years of age.Conclusions: Long-term traffic-related exposures were associated with subclinical markers of atherosclerosis. Prospective studies are needed to confirm associations and further examine differences among population subgroups.

BACKGROUNDThe compounds in cigarette smoke are believed to cause oxidative stress, leading to endothelial dysfunction. Understanding the mechanism of endothelial dysfunction due to cigarette smoke is useful for the development of early and preventive therapy for cardiovascular diseases (CVDs) with smoking risk factors.METHODSIn this experimental study, a posttest-only control group design was used. 20 Wistar rats were divided into two groups: a smoking group (exposed to 40 cigarettes per day for 4 weeks) and a control group. After the exposure, the animals were sacrificed and aortas were removed for measurement of malondialdehyde (MDA), superoxide dismutase (SOD), endothelial nitric oxide synthase (eNOS), intima-media thickness (IMT), and for histological analysis.RESULTSExposure to cigarette smoke caused a significant decrease in SOD activity (24.28 ± 4.90; P = 0.027) and eNOS levels (50.81 ± 4.18; P = 0.014), but no significant effect on the level of MDA (17.08 ± 5.78; P = 0.551). Histological analysis showed an increase in IMT (13.27 ± 2.40; P = 0.000) and disorganization and vacuolation of smooth muscle cells in tunica media after exposure to cigarette smoke. The regression analysis showed a significant negative relationship between the eNOS level and IMT (β = -1.012, P = 0.009).CONCLUSIONSubchronic exposure to cigarette smoke caused a decrease in SOD activity and eNOS levels, but no significant change in MDA levels. This study also indicated that smoking causes IMT thickening and pathological structural changes in the aorta. Another finding indicated that a decrease in eNOS levels could cause an increase in the IMT of the aorta.

RationaleThe association between life course socioeconomic position (SEP) and subclinical atherosclerosis is not consistent across studies. Socioeconomic adversities early in life are related to an increased probability of a low occupational grade and more stressful jobs in adulthood. However, the role of job stress in explaining the life course social gradient in subclinical atherosclerosis is unknown. ObjectivesTo examine whether life course SEP is associated with carotid intima-media thickness (IMT) and to investigate whether this association is partially mediated by job stress. MethodsThis study used baseline data (2008–2010) for 8806 current workers from ELSA–Brasil. Maternal education, social class of first occupation and social class of current occupation were used to evaluate childhood, youth and adulthood SEP, respectively. Accumulation of risk across the life course was also evaluated. Job stress was assessed by the Swedish Demand–Control–Support Questionnaire. Directed acyclic graph and linear regression models were used. ResultsLow childhood SEP was associated with increased IMT only in women, but low youth and adulthood SEP were associated with higher IMT in both genders. The simultaneous adjustment for all SEP indicators showed that only adulthood SEP continued to be associated with IMT. However, higher IMT values were observed among men and women sequentially exposed to low SEP in more than one period of life. High-strain jobs and low job control were not associated with IMT independent of SEP. ConclusionOur results support a model of the cumulative effects of exposures to SEP across the life span because the highest IMT values were observed in individuals sequentially exposed to low SEP in more than one period of life. We did not find that job stress explained the association between life course SEP and IMT, suggesting that strategies to address socioeconomic inequalities in CVD should target additional steps beyond reducing job stress.

The expanded application of carbon nanotubes and increased annual production has recently sparked public interest concerning associated and potentially adverse exposure effects. As very little is known with regard to the toxicology and underlying mechanism of the phenomena termed "single-walled carbon nanotube (SWCNT) exposure", we conducted an in depth investigation of potential SWCNT effects on cell adhesion molecule gene expression within rat aortic endothelial cells (RAECs). RAEC exposure to SWCNT induced neutrophil adhesion to the endothelial monolayer via increased ICAM-1 and VCAM-1 expression. Due to NF-kappaB's fundamental involvement in the transcriptional regulation of cell adhesion molecules, we studied NF-kappaB/P65 activation in SWCNT treated RAECs, as well as GSH and LDH as determinants of oxidative stress, a condition that influences NF-kappaB activation. Resultant data indicates SWCNT exposure induces oxidative stress, thereby altering ICAM-1 and VCAM-1 expression. SWCNT induced nuclear NF-kB/P65 translocation can be inhibited by N-acetylcysteine, indicating elevated ICAM-1 and VCAM-1 expression is mediated by oxidative stress in RAECs, and may play important inflammatory roles in SWCNT-induced vascular endothelium damage.

TPS 671: Cardiometabolic effects of long-term air pollution exposure, Exhibition Hall, Ground floor, August 26, 2019, 3:00 PM - 4:30 PM Background: Long-term exposure to air pollution increases the risk of cardiovascular morbidity and mortality, but the mechanism is not fully known. It has been suggested that air pollution exposure contributes to the development of atherosclerosis, such as carotid artery plaques, a well known precursor of cardiovascular disease. Methods: A Swedish population-based cohort (age 46–67 years) was recruited within the Malmo Diet and Cancer study between 1991 and 1994, of which 6103 underwent ultrasound examination of the right carotid artery. The definition of carotid artery plaque was “a focal thickening of the intima-media complex of >1.2 mm and with an area of ≥10 mm2”. Also intima-media thickness (IMT) was measured (1 cm proximal to the bifurcation). Participants were assigned individual residential air pollution exposure (source-specific PM2.5, PM10, NOx, BC) at recruitment from Gaussian dispersion models. Logistic and linear regression was used to examine associations between air pollution and the prevalence of carotid artery plaques, and IMT, adjusted for potential confounders and usual cardiovascular risk factors. Results: The prevalence of carotid plaques was 34%. The mean levels of PM2.5 and PM10 at recruitment were about 10 and 14 µg/m3, most of which was due to long range transport. The mean NOx level was 39 µg/m3, most of which was due to local emissions. There was only a limited and non-significant association between PM2.5 and plaque prevalence (OR: 1.07, 95% CI 0.91 – 1.26, per µg/m3), and no association with PM10, NOx or BC. There was also no significant linear trend between plaque and air pollution levels in quartiles. There was a slight positive association between IMT and PM2.5, but not statistically significant. Conclusions: Overall we found only limited support for the hypothesis that air pollution exposure for PM10, PM2.5, BC or NOx increases the risk of atherosclerosis in the carotid arteries.

Occupational exposure to lead may cause an increase in blood pressure. The aim of the study was to estimate the effect of occupational exposure to lead on selected parameters of ambulatory blood pressure monitoring (ABPM) and structural changes in carotid arteries. The study included 33 normotensive men occupationally exposed to lead and 39 unexposed men employed in administration of the foundry. All of the men underwent 24-hour ambulatory blood pressure monitoring and high-resolution B-mode ultrasonography to determine intima-media thickness (IMT). The group of men occupationally exposed to lead manifested significantly higher mean systolic blood pressure (MSBP), mean diastolic blood pressure (MDBP), mean blood pressure (MBP), pulse pressure (PP), variability of diastolic blood pressure (VDBP), and IMT than the unexposed group. The studied groups did not differ in mean values of variability of systolic blood pressure (VSBP). As compared to the unexposed group, in men exposed to lead, atherosclerotic plaques were significantly more common. In the group of persons exposed to lead the Pearson's correlation coefficient analysis revealed significant linear positive correlations between MSBP and IMT, between lead level and the number of atherosclerotic plaques, and between lead level and PP. Multivariate stepwise regression analysis demonstrated that higher lead level in blood and higher triglyceride concentration in blood represent independent risk factors of an increased pulse pressure in the group of individuals occupationally exposed to lead. Occupational exposure to lead can be associated with increased blood pressure and accelerated progression of atherosclerosis.