Mohammad Hashemi

Acute and long-term effects of grape and pomegranate juice consumption on vascular reactivity in paediatric metabolic syndrome

OBJECTIVESnThis study, which to the best of our knowledge is the first of its kind, aimed to determine the acute and long-term effects of the consumption of grape and pomegranate juices on endothelium function in adolescents with metabolic syndrome, and to compare the effects of these two kinds of juices.nnnMETHODSnThis randomised controlled clinical trial was conducted in 2008 among 30 adolescents, aged 12-15 years, with metabolic syndrome. Participants were randomly assigned to two groups of equal number; one group was asked to drink 18 millilitre per kilogram per day of natural grape juice and the other group was asked to drink 240 millilitre per day of natural pomegranate juice once daily for 1 month. Juices were homemade without any added sweetener. Basal brachial artery dimension and flow-mediated dilation as an index of endothelial function and endothelial-dependent dilation after receiving nitoglycerin spray were evaluated by high-resolution B mode ultrasonography before juice consumption, 4 hours and 30 days after regular daily consumption.nnnRESULTSnFlow-mediated dilation at 90 seconds and after nitoglycerin significantly improved at 4 hours and at 1 month after drinking both kinds of juices, without significant difference between the two groups. The change at 1 month versus 4 hours was significant only in the grape juice group.nnnCONCLUSIONnDaily consumption of diets rich in antioxidants might improve endothelial function in adolescents with metabolic syndrome. These effects began as soon as 4 hours after juice consumption. Such beneficial effects should be considered in dietary recommendations for the paediatric age group, notably in obese individuals.

Long-term effect of enhanced external counterpulsation on endothelial function in the patients with intractable angina.

BACKGROUNDnEnhanced external counterpulsation (EECP) is a noninvasive, pneumatic technique that provides favourable effects in patients with coronary artery disease. The objective of this study was to describe the long-term effect of EECP on endothelial function in patients with ischaemic cardiomyopathy.nnnMETHODnThe study was performed in 15 patients with ischaemic cardiomyopathy. All subjects were treated with EECP 1-h per day, 5 days a week, over 7 weeks (totally 35h). Endothelium-dependent and -independent relaxation was assessed by flow-mediated dilation (FMD) and nitroglycerine-mediated dilatation (NMD). In each patient, FMD and NMD measurements were performed before, at midcourse (day 17th) and after completion of EECP course (day 35th). In addition, FMD index was assessed 1 month after completion of EECP therapy.nnnRESULTSnResults showed that EECP was associated with a significant improvement in FMD index after 35 hours of EECP (10.95+/-4.1% vs. 7.40+/-4.9% for baseline, p<0.05). NMD index didnt significantly alter during the EECP therapy. Also, 1 month after completion of EECP, FMD index returned to baseline (7.51+/-4.4% vs. 7.40+/-4.9%, respectively, p<0.05). EECP acutely improved endothelial function in ischaemic cardiomyopathic patients. However, after 1 month completion of treatment, endothelium-dependent vasorelaxation returned to baseline.nnnCONCLUSIONnIt seems that improvement of endothelial function is not the main mechanism of long-term EECP treatment and other mechanisms should be considered.

Effect of particulate air pollution and passive smoking on surrogate biomarkers of endothelial dysfunction in healthy children

Abstract Background: This study aimed to determine the association of ambient particulate matter (PM) on surrogate markers of endothelial function and inflammation in healthy children with or without exposure to second-hand smoke. Methods: This cross-sectional study was conducted in 2011 in Isfahan, which is the second largest and second most air-polluted city in Iran. The areas of the city with lowest and highest air pollution were determined, and in each area, 25 pre-pubescent boys with or without exposure to daily tobacco smoke at home were selected, i.e. 100 children were studied in total. Serum levels of C-reactive protein (CRP) and nitric oxide (NO) were measured. Results: Mean (SD) NO concentration was 7·87 (2·18) and 7·75 (2·04) μmol/L for participants not exposed and exposed to passive smoking, respectively, which is not statistically significant. The corresponding figures for CRP concentrations were 1·69 (0·89) and 2·13 (1·19) μg/ml (Pu200a=u200a0·04). Mean (SD) CRP concentration was significantly higher in children living in the highly polluted area than in those in the area of low pollution [2·11 (1·91) vs 1·60 (1·43) μg/ml, respectively, Pu200a=u200a0·02]. This difference was not significant for NO concentration. The regression analysis that examined the association between PM concentration (as independent variable) and CRP and NO levels (as dependent variables) in children not exposed to passive smoking demonstrated that increased PM was associated with a decrease in NO and an increase in CRP concentration. This finding shows that, regardless of passive smoking, PM10 concentration has a significant independent association with serum CRP and is inversely associated with NO levels. Conclusion: The findings suggest that in healthy children PM concentration has a significant independent association with biomarkers of endothelial dysfunction and inflammation.

Dietary fatty acids and inflammatory markers in patients with coronary artery disease.

Background: Atherosclerosis, with its major manifestation, coronary artery disease (CAD) is a chronic inflammatory disease. Dietary fatty acids intakes favorably effect on inflammatory responses. This study was conducted to examine the association between dietary fatty acid intakes and inflammatory markers, interleukin 6 (IL-6) and high sensitivity C-reactive protein (hs-CRP), in CAD patients among Iranian population. Materials and Methods: This hospital-based, cross-sectional study was conducted in Chamran Heart Hospital, Isfahan, Iran in 2012. Patients aged ≥45 years with first ever symptomatic CAD confirmed by angiography were included. A semi-quantitative food frequency questionnaire (FFQ) was used to assess the usual intakes of dietary fatty acids. Results: The energy-adjusted daily intakes (mean ± SD) of saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), linoleic acid, α-linolenic acid, and eicosapentaenoic acid and docosahexaenoic acid (EPA + DHA) were 27 ± 9, 22 ± 6, 21 ± 5, 0.4 ± 0.32, and 0.85 ± 0.82 g/d; respectively. After adjustment for potential confounders, SFA was directly related to hs-CRP (P = 0.01) and IL-6 (P < 0.001) concentrations. Intakes of EPA + DHA and MUFA, were significantly adversely related to plasma hs-CRP concentration (P = 0.002 and 0.001, respectively) but not IL-6, albeit MUFA was modestly inversely related to IL-6 (P = 0.08). No significant relationships were observed for other fatty acids, α-linolenic acid, and linoleic acid. Conclusions: These findings suggest that saturated fatty acids, EPA + DHA and MUFA were significantly related to plasma inflammatory markers in CAD patients.

Mutations in the Histone Modifier PRDM6 Are Associated with Isolated Nonsyndromic Patent Ductus Arteriosus

Nonsyndromic patent ductus arteriosus (PDA) is a common congenital heart defect (CHD) with both inherited and acquired causes, but the disease mechanisms have remained elusive. Using combined genome-wide linkage analysis and whole-exome sequencing (WES), we identified independent mutations in PRDM6, which encodes a nuclear protein that is specific to vascular smooth muscle cells (VSMC), has histone methyl transferase activities, and acts as a transcriptional suppressor of contractile proteins. Inxa0vitro assays showed that the mutations cause loss of function either by intracellular redistribution of the protein and/or by alteration of its methyltransferase activities. Wild-type embryonic ductus arteriosus (DA) exhibited high levels of PRDM6, which rapidly declined postnatally as the number of VSMCs necessary for ductus contraction increased. This dynamic change suggests that PRDM6 plays a key role in maintaining VSMCs in an undifferentiated stage in order to promote their proliferation and that its loss of activity results in premature differentiation and impaired remodeling of the DA. Our findings identify PRDM6 mutations as underlying genetic causes of nonsyndromic isolated PDA in humans and implicates the wild-type protein in epigenetic regulation of ductus remodeling.

First report on the association of drinking water hardness and endothelial function in children and adolescents

Introduction This study aims to investigate the relationship of water hardness and its calcium and magnesium content with endothelial function in a population-based sample of healthy children and adolescents. Material and methods This case-control study was conducted in 2012 among 90 individuals living in two areas with moderate and high water hardness in Isfahan County, Iran. The flow-mediated dilatation (FMD) of the brachial artery and the serum levels of soluble adhesion molecules (sICAM-1, sVCAM-1) were measured as surrogate markers of endothelial function, and high-sensitivity C-reactive protein (hs-CRP), as a marker of inflammation. Results Data of 89 participants (51% boys, mean age 14.75 (2.9) years) were complete. Those participants living in the area with high water hardness had higher FMD, hs-CRP, and soluble adhesion molecules (sICAM-1, sVCAM-1) than their counterparts living in the area with moderate water hardness. Multiple linear regression analysis showed that after adjustment for confounding factors of age, gender, body mass index, healthy eating index and physical activity level, total water hardness, as well as water content of calcium and magnesium, had a significant positive relationship with FMD. The corresponding associations were inverse and significant with soluble adhesion molecules (p < 0.05). Conclusions This study, which to the best of our knowledge is the first of its kind in the pediatric age group, suggests that water hardness, as well as its calcium and magnesium content, may have a protective role against early stages of atherosclerosis in children and adolescents.

Endogenous expression of the atypical chemokine receptor CCX-CKR (CCRL1) gene in human embryonic kidney (HEK 293) cells

CCX-CKR (CCRL1) as one of the chemokine receptor-like proteins is a scavenger of CCL19, CCL21, CCL25, and CXCL13 chemokines. Human CCX-CKR is expressed in various tissues. Since HEK 293 cells are used for both transient and stable expression of CCX-CKR gene, it is important to determine endogenous expression of CCX-CKR gene. Therefore, in the current study endogenous expression of CCX-CKR gene was evaluated in HEK 293 cells. To test the expression of CCX-CKR gene in HEK 293 cells, total RNA was isolated from HEK 293 cells and RT-PCR reaction was primed with the gene-specific primers. Protein expression is then evaluated by Western blot analysis and flow cytometry. Results of this study show that HEK 293 cells express an endogenous CCRL1 gene only at mRNA level. These data therefore represent the important implications for the use of HEK 293 cells as a host cell system for the study of CCX-CKR.

Is there any association of personality traits with vascular endothelial function or systemic inflammation

Background: Evidences showed association of some personality traits with increased risk of cardiovascular diseases, but mediated mechanisms are not entirely described. In this study, we investigated the association of different personality traits with systemic inflammation and endothelial function as probable mediators. Methods: This cross-sectional study was conducted in 2011 on 40-60 years old employees of an industrial company located in Isfahan city (central Iran). Participants were selected through simple random sampling. Personality types were evaluated using the neuroticism-extroversion-openness personality inventory and systemic inflammatory status was determined with high sensitive C-reactive protein (hs-CRP) level. To evaluate endothelial function flow mediated dilation (FMD) were measured. The obtained data were analyzed with univariate correlation and multiple linear regression tests. Results: A total of 254 cases with mean age of 51.4 ± 6.1 years were evaluated. There was no significant relationship between hs-CRP level and FMD with the personality traits in univariate analysis. In multivariate analysis, no association was found between the scores of personality traits and FMD with controlling the factors such as age, body mass index dyslipidemia, hypertension and diabetes. Only there was an inverse association between conscientiousness score and hs-CRP (β = −0.241, P = 0.013). Conclusions: In our population who were the employees of an industrial company, no relationship was found between specific personality trait and endothelial dysfunction. However, we found that the personality trait of responsibility (conscientiousness) is negatively associated with inflammation. Further multi-center studies and also cohort studies are recommended in this regard.

Double-chimera proteins to enhance recruitment of endothelial cells and their progenitor cells.

BACKGROUNDnEnhanced attraction of selective vascular reparative cells is of great importance in order to increase vascular patency after endovascular treatments. We aimed to evaluate efficient attachment of endothelial cells and their progenitors on surfaces coated with mixture of specific antibodies, L-selectin and VE-cadherin, with prohibited platelet attachment.nnnMETHODSnThe most efficient conditions for coating of L-selectin-Fc chimera and VE-cadherin-Fc chimera proteins were first determined by protein coating on ELISA plates. The whole processes were repeated on titanium substrates, which are commonly used to coat stents. Endothelial progenitor cells (EPCs) and human umbilical vein endothelial cells (HUVECs) were isolated and characterized by flow cytometry. Cell attachment, growth, proliferation, viability and surface cytotoxicity were evaluated using nuclear staining and MTT assay. Platelet and cell attachment were evaluated using scanning electron microscopy.nnnRESULTSnOptimal concentration of each protein for surface coating was 50 ng/ml. The efficacy of protein coating was both heat and pH independent. Calcium ions had significant impact on simultaneous dual-protein coating (P<0.05). Coating stability data revealed more than one year stability for these coated proteins at 4°C. L-selectin and VE-cadherin (ratio of 50:50) coated surface showed highest EPC and HUVEC attachment, viability and proliferation compared to single protein coated and non-coated titanium surfaces (P<0.05). This double coated surface did not show any cytotoxic effect.nnnCONCLUSIONSnSurfaces coated with L-selectin and VE-cadherin are friendly surface for EPC and endothelial cell attachment with less platelet attachment. These desirable factors make the L-selectin and VE-cadherin coated surfaces perfect candidate endovascular device.

Comparison of Serum Apolipoprotein Levels of Diabetic Children and Healthy Children with or without Diabetic Parents

Introduction. The association of diabetes and atherosclerosis with disorders of lipids and lipoproteins, notably high apolipoprotein B (apoB) and low apolipoprotein A1(apoA1) is well established. Because of the beginning of the atherosclerosis process from early life, in this study, the plasma levels of apoA1 and apoB were compared in diabetic children with type I diabetes mellitus(DM), healthy children with diabetic parents (HDPs),and healthy children with nondiabetic parents (HNDPs). Methods. This case-control study was conducted among 90 children aged 9–18 years. Serum levels of apoA and apoB were compared among 30 diabetic children (DM), 30 healthy children with diabetic parents (HDPs), and 30 healthy children with nondiabetic parents (HNDP). Results. The mean serum apoA1 was higher in DM (153 ± 69u2009mg/dL) followed by HNDPs (138 ± 58u2009mg/dL) and HDPs (128 ± 56u2009mg/dl), but the difference was not statistically significant. The mean apoB value in HNDPs was significantly lower than DM and HDPs (90 ± 21u2009mg/dL versus 127 ± 47 and 128 ± 38u2009mg/dL, P < 0.05, respectively). The mean apoB levels in DM (127 ± 47u2009mg/dl) and HDP (128 ± 38u2009mg/dL) were not statistically significantly different (P > 0.05). Conclusions. Diabetic children and healthy children with diabetic parent(s) are at higher risk of dyslipidemia and atherosclerosis. Thus for primordial and primary prevention of atherosclerosis, we suggest screening these children for low plasma apoA1 and high plasma apoB levels.