Sima Allahverdian

Cardiovascular risk factors in an Iranian urban population: Tehran Lipid and Glucose Study (Phase 1)

Summary.Objectives: Coronary artery disease is becoming more prevalent in developing countries, particularly in urban areas. This study was conducted to determine the prevalence of cardiovascular risk factors among Tehran urban population.nMethods: The prevalence and distribution of high blood pressure, cigarette smoking, dyslipoproteinemia, diabetes mellitus, and obesity was determined in 15005 subjects, aged three years and over, selected by cluster random sampling in Tehran urban district-13 between February 1999 to August 2001. Total energy intake, percent of energy derived from protein, carbohydrate, and fat were assessed in a subsidiary of 1474 persons by means of two 24-hour dietary recalls.nResults: In adults, 78% of men and 80% of women presented at least one CVD risk factor. The percentage of adult women with two or more risk factors was significantly greater than the one for men. Prevalence of DM, hypertension, obesity, high TC, low HDL, high TGs, and smoking was 9.8, 20.4, 14.4, 19.3, 32, 5.3, and 22.3%, respectively. In children and adolescents, two or more CVD risk factors were found in 9% of boys and 7% of girls. Prevalence of hypertension, obesity, high TC, low HDL, and high TGs, was 12.7, 5.2, 5.1, 10.2, and 5%, respectively. The mean percentage values of energy intake derived from carbohydrate, protein, and fat were 57.8±6.9, 11.1±1.8, and 30.9±7.2, respectively.nConclusion: The prevalence of cardiovascular risk factors among Tehran urban population is high; particularly of high total cholesterol, low HDL cholesterol levels, and high waist to hip ratio. An effective strategy for life style modification is a cornerstone of a population approach to the cardiovascular risk factors. Moreover, these results will serve as a baseline for assessment of future trends in the risk factors studied.

Contribution of Intimal Smooth Muscle Cells to Cholesterol Accumulation and Macrophage-Like Cells in Human Atherosclerosis

Background— Intimal smooth muscle cells (SMCs) contribute to the foam cell population in arterial plaque, and express lower levels of the cholesterol exporter ATP-binding cassette transporter A1 (ABCA1) in comparison with medial arterial SMCs. The relative contribution of SMCs to the total foam cell population and their expression of ABCA1 in comparison with intimal monocyte-derived macrophages, however, are unknown. Although the expression of macrophage markers by SMCs following lipid loading has been described, the relevance of this phenotypic switch by SMCs in human coronary atherosclerosis has not been determined. Methods and Results— Human coronary artery sections from hearts explanted at the time of transplantation were processed to clearly delineate intracellular and extracellular lipids and allow costaining for cell-specific markers. Costaining for oil red O and the SMC-specific marker SM &agr;-actin of foam cell–rich lesions revealed that 50±7% (average±standard error of the mean, n=14 subjects) of total foam cells were SMC derived. ABCA1 expression by intimal SMCs was significantly reduced between early and advanced atherosclerotic lesions, with no loss in ABCA1 expression by myeloid lineage cells. Costaining with the macrophage marker CD68 and SM &agr;-actin revealed that 40±6% (n=15) of CD68-positive cells originated as SMCs in advanced human coronary atherosclerosis. Conclusions— These findings suggest SMCs contain a much larger burden of the excess cholesterol in human coronary atherosclerosis than previously known, in part, because of their relative inability to release excess cholesterol via ABCA1 in comparison with myeloid lineage cells. Our results also indicate that many cells identified as monocyte-derived macrophages in human atherosclerosis are in fact SMC derived.

Serum lipid levels in an Iranian population of children and adolescents: Tehran lipid and glucose study.

Data from 3148 participants aged 3–19years (1447 males and 1701 females) in the cross-sectional phase of Tehran lipid and glucose study (February 1999–May 2000) were used to determine serum lipid levels [total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)] after 12–14 hours overnight fast. The values were analyzed by sex and age. Mean serum TC concentration was 170 mg/dl. TC was significantly greater in females than males (173 vs. 167 mg/dl, p < 0.05). The 90th and 95th percentiles for serum TC were 211 and 227 mg/dl, respectively. There was a significant decrease in mean TC in males during puberty. Thirty-one percent of population had TC values between 170 and 199 mg/dl and 16% had values of 200 mg/dl or greater. The mean TGs values were 103 for males and 108 mg/dl for females [non-significant (NS)]. The prevalence of high-risk values of TGs increased with age in males, reaching a peak at 17–19years. The mean HDL-C level was 45 mg/dl. Mean HDL-C was highest at 7–10years of age and decreased thereafter. The mean LDL-C was 102 in males and 107 mg/dl in females (NS). Twenty-two percent had LDL-C values between 110 and 129 mg/dl and 17% had values 130 mg/dl or greater. The results showed higher levels of TC, LDL-C and TGs and lower HDL-C in Tehranian children and adolescents than other studies. To design comprehensive public health programs to reduce serum lipid levels among Iranian children and adolescents, underlying factors for the high prevalence of dyslipoproteinemia should be sought.

Dietary Factors and Body Mass Index in a Group of Iranian Adolescents: Tehran Lipid and Glucose Study-2

OBJECTIVEnTo study the prevalence of overweight and obesity in an adolescent population in Tehran and to determine possible association with energy and nutrient intake and distribution of energy over the day.nnnMETHODnA cross-sectional study on 177 boys and 244 girls between 10-19 years old was performed. Overweight and obesity were defined by using recommended body mass index (BMI) cut-off values for adolescents. Total energy intake, percent of energy derived from protein, carbohydrate and fat and percent of energy supplied by each meal and snack were assessed by means of two 24-hour dietary recalls.nnnRESULTSnPrevalence of overweight and obesity was 10.7 and 5.1 in boys and 18.4 and 2.8 in girls, respectively. The composition of diet was not different between overweight/obese and normal weight subjects. BMI was related with breakfast energy percentage in girls (r = -0.18, p < 0.01), with total energy intake in boys (r = 0.23, p < 0.01), and with lunch energy percentage in both sexes. In boys (r = 0.16, p < 0.05) and in girls (r = 0.22, p < 0.01).nnnCONCLUSIONnHigh prevalence of overweight and obesity among adolescents was seen. In boys some relationship between total energy intake, distribution of energy over the day and BMI was seen. In girls BMI was only related with distribution of energy over the day.

ATP-Binding Cassette Transporter A1 Expression and Apolipoprotein A-I Binding Are Impaired in Intima-Type Arterial Smooth Muscle Cells

Background— Accumulation of excess cholesterol by intimal arterial smooth muscle cells (SMCs) contributes to the formation of foam cells in atherosclerotic lesions. The purpose of this study was to examine the expression and activity of ATP-binding cassette transporter A1 (ABCA1) in model intimal and medial arterial SMCs, in human atherosclerotic coronary artery intimal and medial layers, and in human intimal and medial SMCs. Methods and Results— Model intimal arterial SMCs showed increased cholesteryl ester accumulation, absence of apolipoprotein A-I–mediated lipid efflux, markedly diminished ABCA1 expression, and poor apoA-I binding compared with medial-layer SMCs. Total ABCA1 mRNA and SMC-specific ABCA1 protein levels were diminished in the intimal layer compared with the medial layer of atherosclerotic human coronary arteries. Increased expression of ABCA1 by liver X receptor agonist treatment or gene transfection failed to correct apolipoprotein A-I binding, lipid efflux, or high-density lipoprotein particle formation by intima-type SMCs. In addition to impaired ABCA1 expression, intima-type SMCs appear to lack a critical binding factor or factors required for the apolipoprotein A-I–ABCA1 interaction, cholesterol efflux, and high-density lipoprotein particle formation. Conclusion— ABCA1 expression is reduced in cultured model intimal and human atherosclerotic lesion SMCs, suggesting that reduced ABCA1 activity contributes to smooth muscle foam cell formation in the intima.

Coronary artery disease is associated with the ratio of apolipoprotein A-I/B and serum concentration of apolipoprotein B, but not with paraoxonase enzyme activity in Iranian subjects

To determine the association of serum apolipoprotein (apo) A-I and B concentrations, and paraoxonase (PON) high-density lipoprotein (HDL) associated enzyme activity with angiographically determined coronary artery disease (CAD) in Iranian diabetic and non-diabetic CAD patients and non-diabetic control subjects, 251 subjects aged 30-70 years, who underwent their first coronary angiography were matched and randomly assigned into three groups: CAD(+)DM(+), CAD(+)DM(-), and CAD(-)DM(-) (control). Stenosis of > or =50% in one or more coronary arteries was classified as CAD(+). CAD(-) was defined as a maximum stenosis of 10% in any coronary artery. Fasting serum concentrations of cholesterol (TC), triglycerides (TGs), LDL-C, HDL-C, apo A-I/B and PON activity were determined. Apolipoprotein concentrations were measured in a fasting serum sample by immunoturbidometric assay and paraoxonase/arylesterase activities by spectrophotometric assay of p-nitrophenol/phenol production following addition of paraoxon/phenylacetate. Information concerning non-lipid risk factors were collected by questionnaires. No significant difference was observed in HDL-C, LDL-C, apo A-I, and PON/arylesterase activity between the study groups. The values of TC (213+/-38 vs 196+/-45, P<0.05), TGs (209+/-187 vs 151+/-113, P<0.01), apo B (99+/-22 vs 96+/-24, P<0.0001), TC/HDL-C (4.8+/-1.5 vs 4.0+/-1.3, P<0.001) and LDL-C/HDL-C (2.9+/-1.1 vs 2.4+/-1.1, P<0.05) were higher and apo A-I/B (1.7+/-0.4 vs 2.0+/-0.6, P<0.01) was lower in CAD(+)DM(+) patients than in control subjects. In CAD(+)DM(-) group, only the level of apo B (96+/-24 vs 85+/-18, P<0.01), and the ratio of apo A-I/B (1.8+/-0.4 vs 2.0+/-0.6, P<0.01), were significantly higher than those of control group. On multiple logistic regression analysis, the best markers for discrimination between CAD(+) groups and CAD(-) control subjects were the ratio of apo A-I/B in diabetic and apo B in non-diabetic patients. The results suggest that in Iranian diabetic and non-diabetic patients with CAD the concentration of apolipoproteins are better markers than traditional lipid parameters in discriminating between CAD(+) and CAD(-) subjects. Lack of significant difference in PON activity between CAD patients and CAD(-) controls supports the concept of interethnic variability in PON polymorphism and unimodal distribution of its activity in non-Europid populations observed in other studies.

Estimation of Energy Requirements for Adults: Tehran Lipid and Glucose Study

OBJECTIVEnThis study was conducted to determine the energy intake of adult residents of district 13 of Tehran and compare the results with their energy requirements.nnnDESIGNnIn this cross-sectional study, 403 subjects were selected by random sampling, including 145 men and 151 women aged 25-50 years and 57 men and 50 women over 50 years old in the framework of Tehran Lipid and Glucose Study (TLGS).nnnMEASUREMENTSnHeight, body weight, waist and hip circumferences were measured, and the body mass index (BMI) and waist-to-hip ratio (WHR) were calculated. Mean energy requirements for each sex-age group were estimated by multiplying specific coefficients (allocated to each group) by body weight and resting energy expenditure (REE), and the results of both methods were compared with mean energy values recommended by Food and Agriculture Organization (FAO)/World Health Organization (WHO) and the U.S. recommended dietary allowance (RDA). Dietary assessment was performed by 48-hour diet recall. A ratio of energy intake to basal metabolic rate lower than 1.27 was considered as under-reporting. Physical activity was evaluated by standard questionnaire of the Lipid Research Clinics (LRC).nnnRESULTSnWomen were significantly more overweight and obese than men (p < 0.001) and older women were more obese than younger ones (p < 0.05). Only one-third of the study population had adequate physical activity. Women had significantly lower physical activity than men (p < 0.01). Energy requirements for both age and sex groups were lower than recommended daily allowances for energy: men 25-50; 2576 vs. 2900; men > 50: 2155 vs. 2300; women 20-50: 2045 vs. 2200 and women > 50: 1817 vs. 1900 kilocalories (kcal). Reported energy intake of men was higher and that of women was lower than the RDA. Forty percent of women and 14% of men under-reported their energy intake.nnnCONCLUSIONnThe energy requirement of the average Tehranian is lower than daily allowances; conditions of obesity and overweight are more prevalent in women. There is high frequency of under-reporting of energy intake in women. Lifestyle modifications to improve dietary habits and to increase physical activity are recommended to decrease overweight and obesity in urban population of Tehran.

Androgen receptor regulation of the versican gene through an androgen response element in the proximal promoter.

Versican, one of the key components of prostatic stroma, plays a central role in tumor initiation and progression. Here, we investigated promoter elements and mechanisms of androgen receptor (AR)-mediated regulation of the versican gene in prostate cancer cells. Using transient transfection assays in prostate cancer LNCaP and cervical cancer HeLa cells engineered to express the AR, we demonstrate that the synthetic androgen R1881 and dihydrotestosterone stimulate expression of a versican promoter-driven luciferase reporter vector (versican-Luc). Further, both basal and androgen-stimulated versican-Luc activities were significantly diminished in LNCaP cells, when AR gene expression was knocked down using a short hairpin RNA. Methylation-protection footprinting analysis revealed an AR-protected element between positions +75 and +102 of the proximal versican promoter, which strongly resembled a consensus steroid receptor element. Electrophoretic mobility shift and supershift assays revealed strong and specific binding of the recombinant AR DNA binding domain to oligonucleotides corresponding to this protected DNA sequence. Site-directed mutagenesis of the steroid receptor element site markedly diminished R1881-stimulated versican-Luc activity. In contrast to the response seen using LNCaP cells, R1881 did not significantly induce versican promoter activity and mRNA levels in AR-positive prostate stromal fibroblasts. Interestingly, overexpression of β-catenin in the presence of androgen augmented versican promoter activity 10- and 30-fold and enhanced versican mRNA levels 2.8-fold in fibroblasts. In conclusion, we demonstrate that AR transactivates versican expression, which may augment tumor-stromal interactions and may contribute to prostate cancer progression.

Sialyl Lewis X modification of the epidermal growth factor receptor regulates receptor function during airway epithelial wound repair

Background Epidermal growth factor receptor (EGFR) is a major regulator of airway epithelial cell (AEC) functions such as migration, proliferation and differentiation, which play an essential role in epithelial repair. EGFR is a glycoprotein with 12 potential N‐glycosylation sites in its extracellular domain. Glycosylation of EGFR has been shown to modulate its function. Previously, our laboratory demonstrated an important role of the carbohydrate structure sialyl Lewis x (sLex) in airway epithelial repair.

Carbohydrates and Epithelial Repair - More Than Just Post-Translational Modification

Epithelia are the layers of cells that form barriers between external milieu and underlying tissues and thus, are important components of most organs of the body. Epithelial layers of organs, such as the lung, are exposed to various challenges resulting in frequent injury. Epithelial wound healing represents an important process by which repair restores the physical barrier lost as a result of cell damage and apoptosis. The repair of epithelial layers consists of a series of ordered events including epithelial cell spreading, migration proliferation and, differentiation. Carbohydrates attached to cell surface proteins and lipids can modulate the function of structures that they are conjugated to and therefore, can affect cell behavior. Although the basic mechanisms of epithelial repair are not entirely understood, many studies suggest glycoconjugates attached to proteins on the cell surface of epithelial cells play important roles in many of these cellular processes. In the present review, the role of carbohydrates in epithelial repair of different organs, including the sources of epithelial injury and current models of epithelial repair will be discussed with a focus on our understanding of the airway epithelium. With a better understanding of carbohydrates and their role in epithelial repair, new therapeutic targets for diseases involving damage to the epithelium can be identified.