In Vitro Targeted Delivery of Simvastatin and Niacin to Macrophages Using Mannan-Grafted Magnetite Nanoparticles.

Atherosclerosis, a leading cause of mortality worldwide, involves various subsets of macrophages that contribute to its initiation and progression. Current treatment approaches focus on systemic, long-term administration of cholesterol-lowering antioxidants such as statins and certain vitamins, which unfortunately come with prolonged side effects. To overcome these drawbacks, a mannose-containing magnetic nanoparticle (NP) is introduced as a drug delivery system to specifically target macrophages in vitro using simvastatin or niacin and a combinational therapy approach that reduces local inflammation while avoiding unwanted side effects. The synthesized NPs exhibited superparamagnetic behavior, neutrally charged thin coating with a hydrodynamic size of 77.23 ± 13.90 nm, and a metallic core ranging from 15 to 25 nm. Efficient loading of niacin (87.21%) and simvastatin (75.36%) on the NPs was achieved at respective weights of 20.13 and 5.03 (w/w). In the presence of a mannan hydrolyzing enzyme, 79.51% of simvastatin and 67.23% of niacin were released from the NPs within 90 min, with a leakage rate below 19.22%. Additionally, the coated NPs showed no destructive effect on J774A macrophages up to a concentration of 200 µg/mL. Simvastatin-loaded NPs exhibited a minimal increase in IL-6 expression. The low dosage of simvastatin decreased both IL-6 and ARG1 expressions, while niacin and combined simvastatin/niacin increased the level of ARG1 expression significantly. Toxicity evaluations on human umbilical vein endothelial cells and murine liver cells revealed that free simvastatin administration caused significant toxicity, whereas the encapsulated forms of simvastatin, niacin, and a combination of simvastatin/niacin at equivalent concentrations exhibited no significant toxicity. Hence, the controlled release of the encapsulated form of simvastatin and niacin resulted in the effective modulation of macrophage polarization. The delivery system showed suitability for targeting macrophages to atherosclerotic plaque.

Two-Dimensional Transthoracic Echocardiography-Based Diagnosis of Right Ventricular Aneurysm: A Neglected Issue in Patients with Coronary Artery Disease: Case Series and Literature Review.

Right ventricular (RV) aneurysm is a very rare ventricular lesion. An aneurysm is formed mainly as a complication of myocardial infarction (MI). As an RV aneurysm is a potentially life-threatening occurrence, its appropriate diagnosis is of great significance. However, right-sided heart diseases, especially RV aneurysms, have been neglected for years. Recent studies in the literature have elucidated the role of the right side of the heart in patients' prognosis and response to treatment. However, RV aneurysm has been scarcely investigated, and most of the attention has been given to the left ventricular aneurysm in patients with ischemic heart diseases (IHD). Herein, we investigated a total of 625 patients with IHD referred for two-dimensional transthoracic echocardiography (2D TTE), among whom 18 were diagnosed with RV aneurysms through precise examination of several TTE views. The characteristics of these cases, including demographics, medical history, and results of cardiac tests (which the patients underwent previously), were recorded and presented. This study emphasized the importance of performing a meticulous 2D TTE evaluation and a thorough examination of different views by an expert echocardiographer, with special attention to the presence of an RV aneurysm in a patient suffering from IHD who presented either with acute coronary syndrome, including MI, or chronic IHD. The scarcity of information, especially in terms of complications and the most appropriate diagnostic methods, calls for further studies in this regard.

Evaluation of the efficacy of signal-averaged electrocardiogram testing in the cardiac assessment of beta-thalassemia major patients.

BACKGROUND: More than 70% of thalassemia's major mortality is due to the cardiac complications of this syndrome, mostly consequent to myocardial Iron overload; therefore, evaluation of such complications is of utmost importance. T2*MRI is used to assess hepatic and myocardial Iron load in thalassemia patients, which is not always available. Signal-Averaged Electrocardiography is a rather easy method of evaluating major thalassemia patients regarding their risk for sudden cardiac death. METHODS AND MATERIALS: In this cross-sectional study, 48 patients with thalassemia major underwent evaluation with electrocardiography, signal-averaged electrocardiography, echocardiography, T2*MRI, and ferritin level. The association of the existence of ventricular late potentials in SAECG and other cardiac variables was evaluated. Moreover, the association between myocardial and hepatic Iron load and cardiac characteristics was assessed. RESULTS: 48 patients with a mean age of 30.31 ± 7.22 years old entered the study. 27 (56.3%) of the patients had ventricular late potentials, which were associated with myocardial dry Iron weight (P = 0.011). Nonspecific ST-T changes and premature atrial and ventricular contractions were seen more frequently in patients with late potentials (P = 0.002, 0.031, and 0.031, respectively). Patients with higher myocardial and hepatic Iron loads had longer QTc in their 12-lead surface electrocardiograms. CONCLUSION: Patients with ventricular late potentials assessed by SAECG had a higher myocardial Iron load. Higher myocardial Iron load is associated with higher cardiac complications in patients with beta-thalassemia major; therefore, SAECG can be used as a screening test for cardiac complications in beta-thalassemia major patients.

Sildenafil for Primary Prevention of Anthracycline-Induced Cardiac Toxicity: A Phase I/II Randomized Clinical Trial, SILDAT-TAHA6 Trial.

Background: Previous animal studies have shown a protective effect of 5-phosphodiesterase inhibitors on cancer therapeutics-related cardiac dysfunction (CTRCD) of anthracyclines. Aim: The aim of this study was to evaluate the clinical effect of sildenafil on the primary prevention of CTRCD in human. Materials and Methods: In this randomized double-blind clinical trial, the primary end point was efficacy in preventing the reduction of left ventricular ejection fraction (LVEF). The intervention group patients received sildenafil at a dose of 25 milligrams twice a day before starting the chemotherapeutic regimen, and the control group received placebo. All the patients at baseline and after the 6-month follow-up underwent 4D and speckle-tracking echocardiography and cardiac MRI, accompanied by hs-troponin I and NT-Pro-BNP measurement. Results: Sixty patients were enrolled in this study, and data from 52 patients (24 patients in the intervention group and 28 patients in the control group) were used in the final analysis. Our findings showed that in the intervention and control groups, LVEF was dropped from 61.28 ± 7.36 to 51.57 ± 7.67 (difference (D) = -9.71 ± 11.95, p=0.003) and from 57.9 ± 7.29 to 50.2 ± 7.02% (D = -7.7 ± 5.93; p=0.001), respectively (between-group difference = -2.01%, p=0.26). CTRCD was detected in 11 patients in the control group (42.8%) and 10 in the intervention group (41.6%, p=0.51). Conclusion: Consumption of sildenafil for primary prevention of anthracycline-induced cardiac toxicity seems to be unbeneficial. This trial is registered with IRCT20180506039554N1.

Partial recovery of senescence in circulating follicular helper T cells after Dasatinib treatment.

Cellular senescence is an irreversible arrest of cell proliferation triggered by different stimuli, including DNA damage, telomere shortening and oncogenic stress. Senescent cells, by releasing the senescence-associated-secretory-phenotype (SASP), contribute to various diseases pathogenesis. Human atherosclerotic plaque contains cells with multiple markers of senescence that associate with disease severity. We characterized the frequency of senescent cTfh cells and genes expressions before and after treatment with Dasatinib in patients with different degrees of stenosis. Twelve high (≥50%), and twelve low (<50%) stenosis patients and six healthy controls were enrolled. The percentage of senescent CD3+CD4+CXCR5+CD153+CD57+ cells was significantly decreased in Dasatinib treated cells from individuals with low and high stenosis (P = 0.0007 and P = 0.0002, respectively). However, the frequency of total lymphocytes, CD3+ and CD4+ T cells were not significantly different between the groups before and after treatment. The expression levels of P53 (P = 0.0003 and P = 0.0001), P16 (P = 0.0005 and P = 0.0002), p21 (P = 0.0002 and P < 0.0001), SENEX (P = 0.0005 and P < 0.0001) and BCL-2 (P = 0.0005 and P = 0.0002) were decreased in PBMCs of low and high stenosis groups after treatment with Dasatinib, respectively. The percentage of senescent cTfh cells positively correlated with cholesterol (P = 0.034; r = 0.671), C-reactive protein (CRP) (P = 0.029; r = 0.707), Erythrocyte sedimentation rate (ESR) levels (P = 0.030; r = 0.598) and neutrophil counts (P = 0.021; r = 0.799) in patients with high stenosis. The decreased frequency of senescent cTfh cells and the expression levels of senescence genes after Dasatinib treatment in patients with atherosclerosis suggest a role for Dasatinib in partial clearance or rejuvenation of senescent cTfh cells, which may decrease inflammatory mediators and attenuate disease progression.

Frequency of Efficient Circulating Follicular Helper T Cells Correlates with Dyslipidemia and WBC Count in Atherosclerosis.

Background: The significance of cTfh cells and their subsets in atherosclerosis is not well understood. We measured the frequency of cTfh subsets in patients with different degrees of stenosis using flow-cytometry. Methods: Participants included high (≥50%; n = 12) and low (<50%; n = 12) stenosis groups, as well as healthy controls (n = 6). Results: The frequency of CCR7loPD-1hiefficient-cTfh was significantly higher in patients with high stenosis compared to healthy controls (p = 0.003) and correlated with low-density lipoprotein (LDL; p = 0.043), cholesterol (p = 0.043), triglyceride (p = 0.019), neutrophil count (p = 0.032), platelet count (p = 0.024), neutrophil/lymphocyte ratio (NLR; p = 0.046), and platelet/lymphocyte ratio (PLR; p = 0.025) in high stenosis group. The frequency of CCR7hiPD-1lo quiescent-cTfh was higher in healthy controls compared to the high-stenosis group (p = 0.001) and positively correlated with high-density lipoprotein (p = 0.046). The frequency of efficient-cTfh cells was correlated with platelet count (p = 0.043), NLR (p = 0.036), and PLR (p P = 0.035) in low-stenosis group, while that of quiescent-cTfh cells was negatively correlated with LDL (p = 0.034), cholesterol (p = 0.047), platelet count (p = 0.032), and PLR (p = 0.041). Conclusion: High percentages of cTfh and efficient-cTfh cells in patients with advanced atherosclerosis and their correlation with dyslipidemia and white blood cell counts suggest an ongoing cTfh subset deviation, towards efficient phenotype in the milieu of inflammation and altered lipid profile. Efficient cTfh cells have an effector phenotype and could in turn contribute to atherosclerosis progression.

T Cell Proliferative Responses and IgG Antibodies to ß2GPI in Patients with Diabetes and Atherosclerosis.

BACKGROUND: Diabetes increases the risk of myocardial infarction (MI) by 2 to 3 folds. Tlymphocytes play a role in atherosclerosis, which is the main pathology behind MI. Cellular immune responses to beta-2 glycoprotein I (ß2GPI) are shown in carotid atherosclerosis. OBJECTIVE: To investigate the self-reactive, ß2GPI-specific T-lymphocytes in patients with and without diabetes and atherosclerosis. METHODS: Collectively, 164 subjects with and without diabetes that underwent coronary angiography were divided into four groups based on their diabetes status and coronary stenosis. Group I=Diabetic with ≥50% stenosis: A+D+ (n=66); Group II=Non-diabetic with ≥50% stenosis, A+D- (n=39); Group III=Diabetic with <50% stenosis: A-D+ (n=28); and Group IV=Non-diabetic with <50% stenosis: AD- (n=31). All groups were evaluated for anti-ß2GPI IgG antibody by ELISA method. Then, PBMCs were isolated from 18 subjects and were stimulated with ß2GPI-derived peptides to assess their proliferation in accordance with their HLA-DRB1 alleles. RESULTS: Mean ß2GPI IgG levels were higher in groups with ≥50% stenosis (A+) compared to those with <50% stenosis (A-), (P=0.02). The co-presence of diabetes in A+ individuals increased mean ß2GPI-specific IgG. Auto-reactive ß2GPI-specific T cells were detected in the repertoire of T-lymphocytes in all groups. ß2GPI-peptides showed promiscuous restriction by various HLADRB1. CONCLUSION: ß2GPI is the target of cellular and humoral immune responses in patients with atherosclerosis. Since the T cell responses but not antibodies were detectable in A-D+ and A-D- groups, it is reasonable to assume that cellular responses preceded the humoral responses. Post-translation modifications of ß2GPI under oxidative and glycemic stresses may have increased the IgG levels in patients with diabetes. Finally, identification of antigens that trigger immuno-pathogenesis in atherosclerosis and diabetes may help the development of immunomodulation methods to prevent or treat these debilitating diseases.

Increased frequency of HLA-A*02 in patients with atherosclerosis is associated with VZV seropositivity.

BACKGROUND: HLA molecules are inherited key molecules in the immune inflammation and specific responses to environmental pathogens. We investigated the association of HLA-A alleles with Varicella zoster virus (VZV) seropositivity in patients with atherosclerosis (AS). MATERIALS AND METHODS: Plasma Anti-VZV IgG and molecular HLA type were detected in 203 (100 AS+ and 103 AS-) individuals. RESULTS: Of 100 AS+ individuals, 66 were anti-VZV+ and 34 were anti-VZV-. Of 103 age/sex-matched AS- individuals, 59 were anti-VZV+ and 44 were anti-VZV-. Anti-VZV-IgG in AS+ cases was higher than AS- controls (p = .034). The mean anti-VZV IgG in HLA-A*02+AS+ individuals was higher than HLA-A*02+AS- controls (p < .001). HLA-A*02 was associated with VZV-seropositivity (p = .01) in AS+ patients. A higher frequency of HLA-A*02-allele in AS+ patients compared to AS- controls (p = .015) and an accumulation of HLA-A*02-allele in AS+ anti-VZV+ group (33.3%, p = .004) was observed. CONCLUSIONS: HLA-A alleles and immune responses to VZV are associated with clinical atherosclerosis.

Functional subsets of circulating follicular helper T cells in patients with atherosclerosis.

Frequencies of circulating T follicular helper (cTfh) functional subsets vary in autoimmune diseases. We evaluated the frequencies and clinical relevance of functional subsets of cTfhs in patients with different degrees of stenosis. Blood samples were collected from high (≥50%) (n = 12) and low (<50%) stenosis (n = 12) groups and healthy controls (n = 6). Three subsets of cTfh cells including cTfh1 (CXCR3+ CCR6- ), cTfh2 (CXCR3- CCX6- ), and cTfh17 (CXCR3- CCR6+ ) were detected by flow cytometry. The frequency of cTfh1 cells was higher in control (p = .0006) and low-stenosis groups (p = .005) compared to high-stenosis group. The percentages of cTfh2 and cTfh17 cells were increased in high-stenosis compared to low-stenosis (p = .002 and p = .007) and control groups (p = .0004 and p = .0005), respectively. The frequency of cTfh1 cells negatively correlated with cholesterol (p = .040; r = -.44), C-reactive protein (CRP) (p = .015; r = -.68), erythrocyte sedimentation rate (ESR) (p = .002; r = -.79), neutrophil/lymphocyte ratio (NLR) (p = .028; r = -.67), and cTfh17 (p = .017; r = -.7244) in the high-stenosis group. The percentages of cTfh2 and cTfh17 cells positively correlated with cholesterol (p = .025; r = .77 and p = .033; r = .71), CRP (p = .030; r = .61 and p = .020; r = .73), ESR (p = .027; r = .69 and p = .029; r = .70), NLR (p = .004; r = .76 and p = .005; r = .74), and with each other (p = .022; r = .7382), respectively, in the high-stenosis group. The increased frequencies of cTfh2 and cTfh17 subsets and their correlation with laboratory parameters in patients with atherosclerosis may suggest their role in promoting the inflammatory response and atherosclerosis progression.

Association of ABCA1 Haplotypes with Coronary Artery Disease.

BACKGROUND: Adenosine triphosphate (ATP)-binding-cassette-transporter-A1 (ABCA1) transports cholesterol from cells into apolipoprotein A1 to form high-density lipoprotein (HDL) cholesterol. METHODS: We investigated the frequencies of ABCA1 functional variants in 273 patients with coronary artery disease (CAD) and 261 age-matched, healthy blood donors in southwest Iran. Sequence-specific primer polymerase-chain reaction (SSP-PCR) and polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) were used for genotyping. RESULTS: Frequencies of the rs2422493-TT genotype and T-allele, rs1800976-GG genotype, and G-allele in the promoter and rs2230806-GG genotype and G allele in the exon of the ABCA1 gene were higher in the patients. Abnormal left ventricular size and left-artery disease correlated with rs2422493-T and rs1800976-G alleles, respectively. Wall-motion abnormalities correlated with the rs1883025-G allele and rs2230806-A allele. Regarding the rs2422493/rs1800976/rs2230806/rs1883025 haplotype, T-G-G-A and T-G-A-A were more frequent in case individuals, whereas C-C-G-G was more frequent in control individuals. CONCLUSIONS: The rs2422493-T allele and the rs1800976-G allele increase the risk of disease, as single polymorphisms and in the haplotype. The effect of the rs1883025-G allele is prominent in the haplotype, rather than individually. Considering that G allele of rs2230806 in the third place is present in both susceptible and protective haplotypes, the susceptibility haplotype can be defined as T-G-X-A.

Immune-Inflammation in Atherosclerosis: A New Twist in an Old Tale.

BACKGROUND AND OBJECTIVE: Atherosclerosis, a chronic and progressive inflammatory disease, is triggered by the activation of endothelial cells followed by infiltration of innate and adaptive immune cells including monocytes and T cells in arterial walls. Major populations of T cells found in human atherosclerotic lesions are antigen-specific activated CD4+ effectors and/or memory T cells from Th1, Th17, Th2 and Treg subsets. In this review, we will discuss the significance of T cell orchestrated immune inflammation in the development and progression of atherosclerosis. DISCUSSION: Pathogen/oxidative stress/lipid induced primary endothelial wound cannot develop to a full-blown atherosclerotic lesion in the absence of chronically induced inflammation. While the primary inflammatory response might be viewed as a lone innate response, the persistence of such a profound response over time must be (and is) associated with diverse local and systemic T cell responses. The interplay between T cells and innate cells contributes to a phenomenon called immuneinflammation and has an impact on the progression and outcome of the lesion. In recent years immuneinflammation, an old term, has had a comeback in connecting the puzzle pieces of chronic inflammatory diseases. CONCLUSION: Taking one-step back and looking from afar at the players of immune-inflammation may help us provide a broader perspective of these complicated interactions. This may lead to the identification of new drug targets and the development of new therapies as well as preventative measures.

Interleukin-17 production by CD4+CD45RO+Foxp3+ T cells in peripheral blood of patients with atherosclerosis.

INTRODUCTION: T regulatory cells (Tregs) are known as immunoregulatory cells that are reduced in atherosclerosis. Tregs are a part of crosstalk between the immune system and lipoprotein metabolism, both of which are involved in atherosclerotic processes. Depletion of Tregs leads to impaired clearance of low density lipoprotein (LDL), and intracellular cholesterol homeostasis affects Treg cell development. Furthermore, the atherosclerotic environment affects the Treg cells' phenotype and plasticity. Plasticity between Tregs and Th17 cells has been a matter of investigation lately. We investigated the frequency of interleukin-17 (IL-17)-producing Tregs in the peripheral blood of patients with atherosclerosis. MATERIAL AND METHODS: We studied 10 non-diabetic patients with significant coronary artery disease (CAD) as the patient group, and seven non-diabetic individuals with normal coronary angiography/insignificant CAD as the control group. Peripheral blood mononuclear cells were stained with fluorescent antibodies to detect CD4, CD45RO, IL-17, and Foxp3 expression both before and after stimulation with PMA/Ionomycin. Cell enumeration was performed using flowcytometry and analysed using Mann-Whitney test. RESULTS: CD4+IL-17+Foxp3+ and CD4+IL-17+Foxp3- subsets showed higher frequencies in patients than in controls both before (p = 0.0031, p = 0.033, respectively) and after stimulation (p = 0.0027 and p = 0.0013, respectively). Interestingly, CD4+IL-17+Foxp3+ cells were almost exclusively CD45RO+ with a much higher frequency in patients than in controls (p = 0.0027, p = 0.0007). After stimulation, the frequency of CD4+CD45RO+IL-17+Foxp3+ lymphocytes increased to a greater extent in patients (p < 0.0001) than in controls. CONCLUSIONS: Interleukin-17 production by an intermediate population with an activated Treg phenotype in our patients may point to the population heterogeneity or plasticity in Tregs during atherosclerotic inflammation.

Anti-varicella Zoster Virus IgG and hsCRP Levels Correlate with Progression of Coronary Artery Atherosclerosis.

The relationship between high levels of anti-Varicella Zoster Virus (VZV) IgG in cerebrospinal fluid (CSF) and cerebrovascular atherosclerosis commends a possible similar association in other vessels. We aimed to investigate the association of VZV-seropositivity with coronary artery atherosclerosis. We recruited 88 newly diagnosed patients with more than 50% stenosis in at least one of the main coronary arteries. As the control group, 99 age-matched individuals with normal/insignificant coronary artery findings were included. Clinical, paraclinical, and demographical data were gathered at the time of sampling. High-sensitivity C-reactive protein (hsCRP) levels were measured by nephelometry. VZV-seropositivity was determined by measuring of anti-VZV IgG level in plasma. Multivariable logistic regression was used to evaluate the correlation of data with coronary vascular atherosclerosis. The frequency of VZV-seropositivity was significantly higher in the atherosclerosis group compared to the controls (OR=1.88; 95%CI=1.03-3.44). The plasma levels of anti-VZV IgG were significantly higher in patients with atherosclerosis (Median=2.70, IQR=1.53-4.30 AU/mL) than in the controls (Median=2.10, IQR=1.70-3.10 AU/mL, p=0.034). The hsCRP levels in patients and controls were 5.19±2.00 and 1.51±1.07 mg/L, respectively. The correlation between hsCRP and anti-VZV IgG level in plasma was observed (r=0.40, p<0.001). The levels of hsCRP and anti-VZV IgG increased based on the number of diseased vessels but only the difference in hsCRP levels reached a significant level (p<0.001 and p=0.168, respectively). Our data suggest that VZV-seropositivity and hsCRP elevation jointly increase the risk of atherosclerosis. The multifactorial nature of atherosclerosis; however, leaves more options for the inflammatory milieu to be generated.

Lower Frequency of HLA-DRB1*01 in Southwestern Iranian Patients with Atherosclerosis.

BACKGROUND: Human leukocyte antigen (HLA) complex is a gene family involved in antigen presentation associated with protection or susceptibility to inflammatory, infectious and autoimmune diseases. Atherosclerosis is a chronic inflammatory disease in which HLA molecules play a role in the initiation and development of the disease through presentation of self or foreign antigens to T cells. OBJECTIVE: To investigate the association of HLA-DRB1 alleles with atherosclerosis in a sample of southwestern Iranians. METHODS: We performed an analytical cross-sectional study involving 96 patients with atherosclerosis and 72 controls. HLA-DRB1 genotyping was performed by PCR-SSP method. RESULTS: We observed a significantly lower frequency of DRB1*01 in patients with coronary artery atherosclerosis than in controls (4.68% vs. 13.1, P=0.0052, OR=3.09, CI 95%: 1.35-7.05). However, this allele showed a positive association with high blood pressure (P=0.009) in patients. Furthermore, DRB1*16 allele was associated with hyperlipidemia (P=0.008) in patients. CONCLUSION: Our results demonstrated that DRB1*01 may be a protective allele against atherosclerosis in individuals who live in southwest of Iran. The mechanism of this protection needs further investigation.

Accuracy of exercise tolerance test in the diagnosis of coronary artery disease in patients with left dominant coronary circulation.

BACKGROUND: Exercise is a physiologic stress that helps the physicians to clarify the presence or absence of cardiovascular disease which may be obscure at rest. Although it is sensitive, its specificity is affected by several parameters, such as some metabolic conditions, some structural heart diseases, and some baseline electrocardiogram abnormalities. Currently, the relationship between coronary dominance and accuracy of EET is not examined. Therefore, this study was conducted to determine the potential impact of coronary dominance on the accuracy of EET. METHODS: In this retrospective study, data were gathered from 720 patients from four medical centers. The pattern of dominancy was determined, and the coronary dominance pattern of the patients who had normal angiograms despite abnormal EETs was compared to that from all the patients. RESULTS: Among the patients who had a normal angiogram despite an abnormal EET, 27% were left dominant while the frequency of left dominancy in the whole population of the study was only 10.9% (P=0.013). There were no significant differences in baseline characteristics, such as age and sex, between the two studied groups. CONCLUSION: The results indicated that the presence of left dominance in patients who had normal angiograms despite an abnormal EET was significantly higher than general population. Therefore, left dominance may be considered a confounding factor for EET, producing false positive results.

Resting and Activated Natural Tregs Decrease in the Peripheral Blood of Patients with Atherosclerosis.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease affecting large and medium arteries. CD4+ T cells are known to play a role in the progression of the disease. CD4+CD25+Foxp3+ natural Treg (nTreg) cells seem to have a protective role in the disease and their reduction in acute coronary syndrome is recently shown. OBJECTIVE: To investigate the frequency of nTreg subsets in the peripheral blood of patients with atherosclerosis. METHODS: Confirmation of atherosclerosis was done by angiography and 15 ml heparinized blood was obtained from each of the 13 non-diabetic patients and 13 non-diabetic, non-smoker individuals with normal/insignificant coronary artery disease confirmed by angiography. Lipid profiles of the patients and controls were measured at the time of sampling. Mononuclear cells were used for both RNA extraction and immunophenotyping by real-time PCR and flowcytometry techniques, respectively. RESULTS: In natural Treg subsets, the frequency of CD4+CD45RO-CD25+Foxp3lo T-cells (resting nTregs) was greater in controls than patients (p=0.02). The frequency of CD4+CD45RO+CD25hiFoxp3hi T-cells (activated nTregs) was significantly higher in controls compared with patients (p=0.02). However, the frequency of CD4+CD25+CD45RO+Foxp3- T-cells (effector/memory T-cell) increased in patients compared with controls (p=0.01). Both the MFI and gene expression of Foxp3 were higher in control group than in patients (p=0.015 and p=0.017, respectively). Moreover, the TGF-ß gene expression showed a decrease in the peripheral blood mononuclear cells of patients compared with controls (p=0.03). CONCLUSION: Decrease in both subsets of resting and activated nTregs along with a decrease in the expression of Foxp3 and TGF-ß genes in patients with atherosclerosis suggests phenotypic changes in these subsets, which may as well be correlated with a more inflammatory profile in their lymphocytes.

Correlation of Early and Late Ejection Fractions with CCL5 and CCL18 Levels in Acute Anterior Myocardial Infarction.

BACKGROUND: Acute Myocardial Infarction (AMI) is the leading cause of disability and death in Iran and many other countries. OBJECTIVE: To investigate the prognostic value of CCL5 and CCL18 in patients with acute myocardial ischemia. METHODS: In this cohort study we recruited and followed 50 patients with acute anterior myocardial infarction (AAMI) for developing cardiovascular accidents in a 6-month period. CCL5 and CCL18 levels were measured on admission, at day 5 and at day 180 post-hospitalization. RESULTS: CCL18 and CCL5 levels at day 180 were higher in patients with late (day 180) and early (day 5) LVEF less than 35% compared to those with higher LVEF (p=0.05 and p=0.042, respectively). There was a negative correlation between early and late LVEF and regional wall motion abnormalities (p=0.001 and p=0.002, respectively). There was also a trend of negative correlation between CCL18 levels at day 5 and LVEF levels at day 180 post-hospitalization (p=0.06). CONCLUSION: CCL18 has a correlation with cardiac function in patients with AAMI and it might be considered as an indicator of poor LVEF in patients with AAMI.

Outcome and graft patency in coronary artery bypass grafting with coronary endarterectomy.

BACKGROUND: Controversy persists regarding the use of coronary endarterectomy (CE) in patients with severe coronary artery disease. We compared the comorbidities and perioperative characteristics of patients undergoing coronary artery bypass grafting (CABG) with and without CE. METHODS: This study was performed in two private hospitals in Shiraz, Iran from May 2010 to December 2011 on 967 patients who underwent CABG without CE and 84 patients who underwent CABG with CE (the CE+ group). After follow-up at 9.66±3.65 months post-surgery, 28 patients from the CE+ group underwent angiography to evaluate the patency of grafts and native coronary vessels. RESULTS: Patients in the CE+ group had a more prevalent history of diabetes (48% vs. 36%) and number of diseased vessels (2.88±0.39 vs. 2.70±0.85). The overall hospital mortality was 1.8%, and no significant difference was observed between the two groups. In the 28 patients who underwent reangiography, 113 vessels were bypassed and 29 endarterectomies were performed, mostly on the left anterior descending artery (12 endarterectomies) and the right coronary artery (8 endarterectomies). In the endarterectomized vessels, a 66% patency rate was found in both the grafts and the native vessels. The native coronary vessels were more likely to be patent when the left internal mammary artery was used as a conduit than when a saphenous vein bypass graft was used. CONCLUSION: The lack of a significant difference in postoperative complications in patients who underwent CABG with or without CE may indicate that CE does not expose patients to a higher risk of complications. Since most of the endarterectomized vessels were shown to be patent during the follow-up period, we propose that endarterectomy is a viable option for patients with severely diseased vessels.

QT Dispersion in Young, Ideal, and Old Aged Pregnancies.

BACKGROUND: Obstetricians regard maternal age of 20 to 35 years as the optimal age for pregnancy. Adolescent pregnancy and pregnancy at the ages of 35 years and above are associated with higher risks. Pregnancy is pro-arrhythmic and rarely precipitates ventricular arrhythmias. OBJECTIVES: QT dispersion is an index of heterogeneity of ventricular repolarization and a predictor of propensity of ventricular arrhythmias. In this study, this index was used to find any relationship between maternal age and ventricular arrhythmia risk. METHODS: This study was performed among a group of healthy pregnant ladies between 36 and 40 weeks of gestation. An ECG was taken from each patient. QT dispersions were calculated on a computer screen with high magnitude. The results were then divided into three groups based on the age of the participants. The first, second, and third groups included the women below 20, between 20 and 35, and over 35 years, respectively. The three groups were compared using Kruskal-Wallis test. RESULTS: The mean QTd was 61.77 ms (± 16.61) in the first group, 64.15 ms (± 18.65) in the second group, and 55.95 ms (± 23.04) in the third group. Although QTd was prolonged in all, no significant difference was observed among the three groups regarding QTd. CONCLUSIONS: Our results showed QT prolongation in pregnancy, but showed that maternal age did not affect the heterogeneity of ventricular repolarization and propensity of ventricular arrhythmias in pregnancy.

Can dental pulp calcification predict the risk of ischemic cardiovascular disease?

OBJECTIVE: To report the association of pulp calcification with that of cardiovascular disease (CVD) using digital panoramic dental radiographs. MATERIALS AND METHODS: Digital panoramic radiographs of patients referred from the angiography department were included if the patient was under 55 years old and had non-restored or minimally restored molars and canines. An oral and maxillofacial radiologist evaluated the images for pulpal calcifications in the selected teeth. The sensitivity, specificity, positive predictive value and negative predictive value of panoramic radiography in predicting CVD were calculated. RESULTS: Out of 122 patients who met the criteria, 68.2% of the patients with CVD had pulp chamber calcifications. Pulp calcification in panoramic radiography had a sensitivity of 68.9% to predict CVD. CONCLUSION: This study demonstrates that patients with CVD show an increased incidence of pulp calcification compared with healthy patients. The findings suggest that pulp calcification on panoramic radiography may have possibilities for use in CVD screening.