In vivo, histopathological evaluation, and molecular docking of the antiatherosclerotic potential of Pangium edule leaf extract in cholesterol- and fat-enriched diet Wistar rats

Obesity, an epidemic in children in the United States and abroad, is associated with risk factors for cardiovascular disease (CVD). Less is known about the consequences of morbid obesity in children. In the rural Appalachian population, obesity rates have reached such high proportions that it is difficult to target individual children. Consequently, there is a need to determine whether the morbid obesity category is useful for recommending comprehensive assessment and intervention for the highest risk children. Results from the Coronary Artery Risk Detection In Appalachian Communities (CARDIAC) program informed the use of the morbidly obese category of body mass index (BMI) as a surrogate measure of CVD risk. A total of 23 263 5th grade West Virginia students in the United States participated in a comprehensive risk factor screening between 2003 and 2008. Screening included the calculation of BMI, resting blood pressure, presence of acanthosis nigricans, and fasting lipid profile (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides). Six percent of participants were morbidly obese (BMI >99%). The morbidly obese category provided additional risk factor information than that provided by typically given weight categories, in addition to being a highly specific indicator of additional CVD risk factors. These findings suggest that children diagnosed as morbidly obese have significantly greater chance of experiencing various CVD risk factors than those without morbid obesity diagnosis; these results suggest that the morbidly obese BMI category can be effectively used to target those children at greatest risk when resources are limited.

Analysis of the coordinate expression of 3-hydroxy-3-methylglutaryl coenzyme A synthase and reductase activities in Chinese hamster ovary fibroblasts

The atypical presentation of the metabolic syndrome components in black African women: the relationship with insulin resistance and the influence of regional adipose tissue distribution

Changes in the activities of acetyl-CoA carboxylase and HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase were studied in primary cultures of adult-rat hepatocytes after exposure of the cells to insulin and/or carbohydrates. To determine the contribution of protein synthesis to changes in enzyme activity, the relative rate of synthesis of each enzyme was measured and the amount of translatable mRNA coding for the enzymes was determined by translation in vitro and immunoprecipitation. Addition of insulin to the culture medium increased the activities of acetyl-CoA carboxylase and HMG-CoA reductase by approx. 4- and 3-fold respectively. Although similar increases in the relative rate of synthesis of each protein and template activity were noted, initial increases in the activity of each enzyme occurred before any changes in protein synthesis were observed, suggesting the involvement of post-translational modification of enzyme activity in addition to changes in protein synthesis. The addition of fructose to the culture medium, in the absence of insulin, increased the activity of the carboxylase and the reductase approx. 3-fold, similar to the effects of insulin. However, the effect of fructose was to increase the rate of synthesis and the amount of translatable mRNA coding for acetyl-CoA carboxylase, whereas the increase in the activity of HMG-CoA reductase was not accompanied by any changes in the rate of synthesis or template activity. The effects of fructose could not be mimicked by glucose unless insulin was also present in the culture medium. Similar to observations in vitro, the injection of insulin or the feeding of a high-fructose diet to rats made diabetic by the injection of streptozotocin produced an increase in the activities of acetyl-CoA carboxylase and HMG-CoA reductase, and only the increase in the activity of the carboxylase was accompanied by an increase in the amount of translatable mRNA coding for the enzyme. The results are discussed in terms of the effects of fructose on the synthesis of enzymes involved in lipogenesis.

The purpose of this investigation was to determine if waist-to-height ratio (WHTR) or body mass index (BMI) is the better indicator of cardiovascular disease risk in children and adolescents of varying ages. Data from children and adolescents (N = 2300) who were part of the 2003-2004 National Health and Nutrition Examination Survey (NHANES) were analyzed. Chi-square analyses (2 × 2) were used to compare risk levels of WHTR (>0.50) and BMI (>85th percentile) to systolic blood pressure (SBP) (>90th percentile) as well as total cholesterol (TC) (>200 mg(.) dL(-1) ) for the entire cohort and specified age groups. Significant relationships were detected between SBP and WHTR and BMI, respectively, for the entire cohort as well as the 2 oldest subsamples. A significant association was also noted for both WHTR and BMI to TC for the entire sample and the eldest age group. A significant association was observed between indicators of cardiovascular health risk and both WHTR and BMI in the entire NHANES cohort of boys and girls as well as in the older age groups. The younger groups of participants did not display a notable link between these cardiovascular indicators and WHTR or BMI.

In their article “Targeting Household Air Pollution for Curbing the Cardiovascular Disease Burden: A Health Priority in Sub-Saharan Africa,” Noubiap and colleagues review the literature on household air pollution (HAP) and cardiovascular diseases.1 They point to the lack of studies on cardiovascular events in sub-Saharan Africa and other regions where cooking and heating with solid fuels is common. They also review studies of exposure to cigarette smoke and urban air pollution (mostly in high-income countries) and associated cardiovascular endpoints, including studies of intermediary indicators of cardiovascular risk such as inflammation, endothelial dysfunction, and heart rate variability. This evidence base contributes to both our knowledge of biological mechanisms linking air pollution and cardiovascular outcomes and appropriate indicators of cardiovascular risk. Linking evidence from urban air pollution and HAP, as the authors suggest, assumes that they are equally harmful to human health. Therefore, what is surprisingly absent from their review is the increasing body of evidence linking HAP with important subclinical indicators of cardiovascular diseases, including blood pressure, which is strongly and directly related to cardiovascular mortality.2 For example, a previous study in rural China found a dose-response relationship between personal exposure to HAP and blood pressure in women cooking with biomass fuels,3 and several cookstove intervention studies in Latin America found lowered blood pressure4-7 and reduced ST-segment depression8 in women with reduced exposure to HAP. Cross-sectional studies in Peru found higher blood pressure and greater prevalence of carotid atherosclerotic plaque among biomass users compared with users of gaseous fuels9, 10 and a small feasibility study in China found some evidence of an association between exposure to biomass smoke and arterial stiffness.11 Controlled evaluations conducted in high-income countries provide further evidence; short-term changes in exposure to woodsmoke were associated with arterial stiffness in a laboratory-based study of healthy Swedish adults12, 13 and an air filtration intervention resulted in improved markers of systemic inflammation and endothelial function (but not oxidative stress) among Canadian adults living in a woodsmoke-impacted community.14 We applaud Noubiap and colleagues for highlighting this important and often underrepresented global health issue to the readership of The Journal of Clinical Hypertension. We particularly appreciate the focus on energy and air pollution in sub-Saharan Africa, where much of the population is heavily impacted by exposure to HAP and its associated disease burden.15 We do, however, feel inclined to draw attention to the important omission of the growing body of research evaluating the association between HAP with these important indicators of cardiovascular disease risk. While it is our hope that this research base should be used to inform future evaluations in all regions of the world, it is certainly worth noting that few studies have been conducted in sub-Saharan Africa. Obtaining direct evidence in this region will have important public health implications and should be heavily prioritized. The authors do not have any conflicts of interest to declare.

Previous reports, based on clinical trials and animal experiments, suggest that beta-blockers may be useful in the prevention of atherosclerosis. Betaxolol, a new beta1-selective blocker, was shown to decrease plasma total and LDL cholesterol levels or to have no adverse effect on those [1-4]. While many reports deal with metabolism of triglyceride and high density lipoprotein, fewer publications about cholesterol metabolism are currently available. To clarify the mechanism by which beta-blockers affect lipid metabolism, we examined the effects of beta-blockers on HMG CoA reductase and LDL receptor activity in cultured human skin fibroblasts. L-propranolol, a nonselective beta-blocker, increased HMG CoA reductase activity and decreased LDL receptor activity. However, d-propranolol had no major effects on HMG CoA reductase activity. These results suggest that beta-blockers act on HMG CoA reductase through the beta receptors. Beta1-blocking action should decrease HMG CoA reductase activity and increase LDL receptor activity. In fact, betaxolol, a beta1-selective blocker, decreased HMG CoA reductase activity and increased LDL receptor activity, but metoprolol had no major effect. We speculate that the discrepancy between betaxolol and metoprolol in the effect on HMG CoA reductase and the LDL receptor might be due to the difference of the extent of beta1-selectivity. We conclude that beta1-selective blockers are antihypertensive agents potentially valuable in the prevention of atherosclerosis.

Dietary Cholesterol Affects Chenodeoxycholic Acid Action on Biliary Lipids

Results from several laboratories clearly indicate that expression of scavenger receptor class B type I (SR-BI) enhances the bidirectional flux of cholesterol between cells and lipoproteins. Because the activity of HMG-CoA reductase, the key enzyme in cholesterol biosynthesis, is regulated by cell cholesterol content, we designed experiments to investigate the effect of SR-BI expression on the activity of this enzyme and on net cellular cholesterol mass. In addition, we compared the function of SR-BI with its human homolog, CD36 and LIMPII analogous 1. Our experiments demonstrate that both receptors enhance the flux of unesterified or free cholesterol bidirectionally, down a concentration gradient. Receptor-mediated cholesterol flux can effectively modulate multiple aspects of cellular cholesterol metabolism, including the pool that regulates the activity of HMG-CoA reductase. We also found that constitutive expression of SR-BI alters the steady state level of cellular cholesterol and phospholipid when SR-BI-expressing cells are maintained in medium containing serum lipoproteins. All of these effects are proportional to the level of receptor on the cell surface. These data indicate that the level of SR-BI expression determines both the rate of free cholesterol flux and the steady state level of cellular cholesterol.

Mortality due to atherosclerosis is very common and the oxidative modification of low-density lipoprotein (LDL) is responsible for the progression of atherosclerosis. Estimation of oxidized LDL (Ox-LDL), myeloperoxidase (MPO), and paraoxonase (PON1) in subjects with elevated LDL and correlation of oxidized LDL with MPO and PON1 was the main objective. Ox-LDL was determined by ELISA. Activity of Myeloperoxidase and Paraoxonase was estimated by spectrophotometric method. LDL and HDL estimations were carried out in the autoanalyser. Significant increase in the myeloperoxidase and Ox-LDL with the significant decrease in the paraoxonase levels were obseved (p<0.001). No significant change in the HDL levels was seen. LDL showed a positive association with MPO and a negative association with Basal Paraoxonase (BPON) in both cases and controls. Ox-LDL also showed a positive association with MPO and a negative association with BPON only in cases, while no significant association was seen in controls. Ox-LDL seems to be a more sensitive indicator of cardiovascular disease risk than either HDL or LDL cholesterol. Measurement of Ox-LDL, /Myeloperoxidase and Paraoxonase may provide additional details in cardiovascular disease risk prediction.

This study investigated the effects of mulberry leaf extract on lipid metabolism in rats fed a high cholesterol diet. Sprague-Dawley male rats weighing 100±10 g were randomly assigned either to one of two normal diet groups, with (NE group) or without (N group) mulberry extract, or one of four high cholesterol groups containing 1% cholesterol and various levels of dietary mulberry leaf extract. The rats fed high cholesterol diets were subdivided into 4 groups according to level of mulberry extract; Mulberry extract free group (HC group), 0.8% mulberry leaf extract group (HCL group), 1.6% mulberry leaf extract (HCM group) and 3.2% mulberry leaf extract (HCH group). The rats were fed their respective diets ad libitum for 4 weeks. The levels of serum triglyceride, total cholesterol and LDL-cholesterol of the HC group were higher than mulberry leaf extract supplemented groups. In contrast, the levels of serum HDL-cholesterol in groups supplemented with mulberry leaf extract were significantly lower than that of HC group. Hepatic total lipids, triglycerides, and cholesterol were significantly higher in the high cholesterol groups compared to those of the normal group, but were lower in the HCL, HCM and HCH groups than in the HC group. HMG-CoA reductase activity was significantly decreased in the HC and HCL groups compared to the normal and NE groups. However, the activities in the HCM and HCH group were similar to that of the normal group. The activity of acyl-CoA-cholesterol acyl transferase (ACAT) was increased in high cholesterol groups compared to the normal group. However, the activity was lower for all of the high cholesterol groups fed mulberry leaf extracts, and was lowest for the highest supplemented group (HCH), with no significantly difference from the normal group. In conclusion, the reduction in serum and hepatic lipid composition by mulberry leaf extract may be due to its modulation of HMG-CoA reductase and ACAT activities.

Copper supplementation of adult men: Effects on blood copper enzyme activities and indicators of cardiovascular disease risk

Adverse childhood experiences (ACEs) are linked to poor adult health outcomes, including cardiovascular disease. However, little is known about its prevalence, specifically in low-income populations. The objective of this study was to estimate the extent of ACEs in a low-income, nonclinical, uninsured adult population and assess the relationship between ACEs and cardiovascular disease risk factors. This study leverages the OHIE's (Oregon Health Insurance Experiment) study population, uninsured adults who were randomly selected to apply for Medicaid, and data collected through in-person health screenings. We objectively measured obesity, cholesterol, blood pressure, and blood sugar. Smoking, physical activity, and history of chronic disease were self-reported. Independent variables were the 10-item ACEs questions covering neglect, abuse, and household dysfunction. The sample consisted of 12 229 low-income, nonelderly uninsured adults who participated in the OHIE health screenings from 2009 to 2010. A total of 5929 (48%) returned a follow-up survey reporting ACEs in 2012. ACEs were more prevalent in low-income adults compared with previous estimates in a general clinical population, with notably high rates of emotional abuse, emotional neglect, and household dysfunction. ACEs were statistically associated with higher rates of obesity, smoking, and physical inactivity, but not high cholesterol or diabetes mellitus. We detected a strong relationship between ACEs and a self-reported history of a hypertension diagnosis but no statistically significant differences in being hypertensive. This study design allowed us to assess the prevalence of ACEs among uninsured low-income adults and the association between ACEs and clinical indicators of cardiovascular disease risk that are difficult to ordinarily observe. Low-income adults have high rates of ACEs than previous prevalence estimates and ACEs were associated with higher rates of multiple cardiovascular disease risk factors. As states continue to expand Medicaid to the previously uninsured, providers may want to consider incorporating trauma-based approaches to care delivery.

Background/Aims Ketogenic diet therapies (KDTs) offer a needed therapeutic option for patients with drug-resistant epilepsy. The current study investigated biochemical and anthropometric indices of cardiovascular disease (CVD) risk in adults with epilepsy treated with KDT over 6 months. Method 65 adults with epilepsy naïve to diet therapy were enrolled in a prospective longitudinal study and instructed on modified Atkins diet (MAD) use. Seizure frequency, anthropometric measures, blood levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoproteins A1 and B, and lipoprotein sub-fractions were assessed at baseline, 3 months, and 6 months. Results Subsequent to study enrollment, 34 participants were lost to follow-up, elected not to start, or stopped MAD prior to study completion, leaving a total of 31 participants in the study at 6 months. Compared to baseline, participants on MAD showed significant reductions in median seizure frequency/week, weight, body mass index, waist and hip circumference, and percent body fat at 3 and 6 months. Compared to baseline, participants on MAD for 3 months showed significantly increased levels of total, small and medium LDL particles, ApoB and ApoB/A1 ratio. At 6 months, only small LDL particles and ApoB levels remained elevated and levels of ApoA1 had risen, suggesting possible compensatory adaptation over time. Conclusions This study provides evidence demonstrating the efficacy and cardiovascular safety of 6 months of MAD use by adults with epilepsy. It also highlights an index of CVD risk – small LDL particles - that should be closely monitored.. Trial registration: ClinicalTrials.gov identifier: NCT02694094..

Little is known regarding cardiovascular disease risk indices in HIV-infected women. This study investigated cardiovascular disease risk indices in 100 consecutively recruited HIV-infected women and 75 healthy female control subjects. Subjects were recruited from hospital- and community-based health care providers. C-reactive protein (CRP), interleukin-6 (IL-6), adiponectin, lipid, and glucose levels were the main outcome measures. CT scan, dual-energy x-ray absorptiometry (DXA), and anthropometry were used to assess body composition. Although similar in age, weight, and racial composition, HIV-infected women demonstrated higher CRP (4.6 +/- 0.7 vs. 2.3 +/- 0.4 mg/L, P = 0.007), IL-6 (2.7 +/- 0.2 vs. 1.8 +/- 0.1 pg/mL, P = 0.02), triglyceride (1.84 +/- 0.21 vs. 0.85 +/- 0.05 mM, P = 0.0002), 2-hour glucose after oral glucose challenge (6.88 +/- 0.22 vs. 5.72 +/- 0.17 mM, P = 0.0003), and fasting insulin (81 +/- 8 vs. 45 +/- 2 pM, P = 0.0002) and lower high-density lipoprotein cholesterol (1.17 +/- 0.03 vs. 1.45 +/- 0.05 mM, P < 0.0001) and adiponectin (5.4 +/- 0.3 vs. 7.6 +/- 0.5 mg/L, P = 0.0001) levels compared with the control population. HIV-infected women had more abdominal visceral fat and less extremity fat by CT and DXA scan and demonstrated a higher waist-to-hip ratio (WHR) than the control population. Within the HIV group, CRP and other indices were significantly related to body composition in stepwise regression models. Among all subjects, WHR, but not HIV status, was significantly related to CRP and other cardiovascular disease risk indices. HIV-infected women demonstrate significantly increased risk factors for cardiovascular disease in association with abnormal fat distribution.