Early Development Of Atherosclerosis Research Articles

OBESITY AND ELEVATED LEVELS OF VON WILLEBRAND FACTOR IN PATIENTS WITH HYPERTENSION AND EARLY CORONARY ATHEROSCLEROSIS

Objective: Obesity is one of the additional risk factors for early development of atherosclerosis and cardiovascular complications in patients with hypertension. Von Willebrand factor (vWF) is a plasma glycoprotein which plays an important role in the thrombogenesis. On the other hand it is considered as a marker of the endothelial dysfunction. The objective of our study was to assess the level of vWF in patients with hypertension and early manifestations of coronary atherosclerosis depending on the presence of obesity. Design and method: 79 middle-age (49,88 ± 7,77) patients with hypertension and established coronary atherosclerosis (71 men and 8 women) were involved into study. According to the calculating body mass index (BMI), all subjects were divided into 2 groups: 22 obese people (BMI above 30 kg/m2) and 57 non-obese patients. In all patients we analyzed family history, smoking status, history of diabetes. The plasma lipid profile and vWF level were estimated using EIA kit (Uscn Life Science Inc., Cloud-Clone Corp., USA). Results: Both groups did not differ in the family history of cardiovascular disease, smoking status and diabetes. Though all patients received statins triglycerides levels were significantly higher in obese patients [95%CI: 1.50; 2.57] compared with patients in the other group [95% CI: 1.29; 1.70] (p < 0.05). Almost all but one obese patient had high levels of vWF [95% CI: 53.87; 72.38]. Among patients with a BMI below 30 kg/m2, normal values of vWF were detected in 21 patients [95% CI: 41.38; 52.76]. The groups significantly differed in the level of vWF, both when calculating the odds ratio (OR) using the Pearson chi-square criterion [OR: 5,6; p = 0.0035] and when comparing samples according to the Student's t-criterion (p < 0.005). Conclusions: Results of the study suggest enhanced endothelial dysfunction as one of the possible links between obesity and increased risk of cardiovascular complications in patients with hypertension.

Artemisinin protects endothelial function and vasodilation from oxidative damage via activation of PI3K/Akt/eNOS pathway.

Previous studies showed that artemisinin (ART) may be useful in the protection against the early development of atherosclerosis, but the effects of ART on vasodilation and eNOS remained unclear. In the current study, we investigated the protective effect of ART on endothelial cell injury induced by oxidative stress and its underlying mechanism via MTT assay, Flow Cytometry Assay, Vasodilation study, Western blotting and vivo assay. We found that pretreatment of human umbilical vein endothelial cells (HUVECs) with ART significantly suppressed H2O2-induced cell death by decreasing the extent of oxidation and MDA activity, activating SOD, increasing NO production and inhibiting caspase 3/7 activity. Meanwhile, we also found that ART was able to activate PI3K/Akt/eNOS pathway. PI3K inhibitor LY294002 or Akt kinase specific inhibitor Akt inhibitor VIII blocked the protective effect of ART. To explore the effect of ART in the damage of vasodilation induced by H2O2 in mice, we treated the aortic ring from C57BL/6 mice with H2O2 with or without ART, the results demonstrated that ART ameliorated endothelium-dependent vasodilation damage induced by H2O2. Taken together, these data suggest that ART is able to protect endothelial function and vasodilation from oxidative damage, at least in part through activation of PI3K/Akt/eNOS pathway. Our findings indicate that artemisinin maybe as a potential therapeutic agent for patients with atherosclerosis.

Insulin Resistance and Ischemic Etiology Heart Failure: Is There an Interrelationship in Clinical Practice?

Background. IR promotes the development of early atherosclerosis and may increase the risk of cardiovascular complications, which is of great importance in patients with CHF. Thus, the assessment of the relationship between IR and clinical indicators of CHF is relevant in the clinical aspect and needs more detailed research. Objective: To evaluate the relationship between IR and clinical parameters in hospitalized ischemic etiology CHF patients without concomitant CMD. Methods. The study included 174 hospitalized patients with a stable course of CHF FC III (NYHA) and CAD from 18 to 65 years old, without previously identified CMD. Anthropological, clinical, laboratory examination was carried out. The neurohormonal profile included insulin (IR by HOMA- IR), aldosterone, and Nt-proBNP levels. To study the relationship of IR with clinical parameters in CHF and CAD patients, a correlation analysis was performed. Results. A statistically significant relationship between IR and the following parameters was revealed: BMI (r = 0.186, p = 0.045), total FINDRISC score (r = 0.386, p = 0.000), SBP (r = 0.247, p = 0.007), DBP (r = 0.173, p = 0.063), HbA1c (r = 0.388, p = 0.000), insulin concentration (r = 0.833, p = 0.000). To identify independent predictors influencing IR, we carried out multivariate linear regression analysis with stepwise inclusion of indicators in the model, in which HOMA-IR was used as a dependent variable, and BMI, total FINDRISK scores, SBP, DBP, HbA1c levels were included as independent variables. It turned out that the independent factors associated with IR are: HbA1c (β = 0.144; p = 0.000) and the FINDRISK scale points (β = 0.064; p = 0.05). Conclusions. In patients with CHF and CAD, IR is interrelated with such indicators as BMI, FINDRISC total points, SBP, DBP, HbA1c. Independent predictors influencing IR are HbA1c and the FINDRISK total points.

Vasculoprotective properties of plasma lipoproteins from brown bears (Ursus arctos)

Plasma cholesterol and triglyceride (TG) levels are twice as high in hibernating brown bears (Ursus arctos) than healthy humans. Yet, bears display no signs of early stage atherosclerosis development when adult. To explore this apparent paradox, we analyzed plasma lipoproteins from the same 10 bears in winter (hibernation) and summer using size exclusion chromatography, ultracentrifugation, and electrophoresis. LDL binding to arterial proteoglycans (PGs) and plasma cholesterol efflux capacity (CEC) were also evaluated. The data collected and analyzed from bears were also compared with those from healthy humans. In bears, the cholesterol ester, unesterified cholesterol, TG, and phospholipid contents of VLDL and LDL were higher in winter than in summer. The percentage lipid composition of LDL differed between bears and humans but did not change seasonally in bears. Bear LDL was larger, richer in TGs, showed prebeta electrophoretic mobility, and had 5–10 times lower binding to arterial PGs than human LDL. Finally, plasma CEC was higher in bears than in humans, especially the HDL fraction when mediated by ABCA1. These results suggest that in brown bears the absence of early atherogenesis is likely associated with a lower affinity of LDL for arterial PGs and an elevated CEC of bear plasma.

Tc17 CD8+ T cells accumulate in murine atherosclerotic lesions, but do not contribute to early atherosclerosis development.

AimsCD8+ T cells can differentiate into subpopulations that are characterized by a specific cytokine profile, such as the Tc17 population that produces interleukin-17. The role of this CD8+ T-cell subset in atherosclerosis remains elusive. In this study, we therefore investigated the contribution of Tc17 cells to the development of atherosclerosis.Methods and resultsFlow cytometry analysis of atherosclerotic lesions from apolipoprotein E-deficient mice revealed a pronounced increase in RORγt+CD8+ T cells compared to the spleen, indicating a lesion-specific increase in Tc17 cells. To study whether and how the Tc17 subset affects atherosclerosis, we performed an adoptive transfer of Tc17 cells or undifferentiated Tc0 cells into CD8−/− low-density lipoprotein receptor-deficient mice fed a Western-type diet. Using flow cytometry, we showed that Tc17 cells retained a high level of interleukin-17A production in vivo. Moreover, Tc17 cells produced lower levels of interferon-γ than their Tc0 counterparts. Analysis of the aortic root revealed that the transfer of Tc17 cells did not increase atherosclerotic lesion size, in contrast to Tc0-treated mice.ConclusionThese findings demonstrate a lesion-localized increase in Tc17 cells in an atherosclerotic mouse model. Tc17 cells appeared to be non-atherogenic, in contrast to their Tc0 counterpart.

Diagnostic Characteristics of Familial Hypercholesterolemia in Children

Familial hypercholesterolemia is autosomal dominant hereditary disorder developing in in humans since birth and it is characterized by low-density lipoproteins concentration increase in blood. Lack of timely diagnostics and therapy for familial hypercholesterolemia is associated with early development of atherosclerosis, cardiovascular pathology and mortality in first 30–40 days of life. Despite the fact that the optimal period for revealing of disease is childhood, diagnostics of the disease has extremely low quality among children. The article presents screening methods and criteria of familial hypercholesterolemia diagnostics among children.

Association of Family History of Cardiovascular Diseases in Boys Aged 12-13 Years with Structural and Functional Indicators of the Left Ventricle and Arterial Stiffness in the Age of 43-46 Years (Results of 32-Year Prospective Follow-up)

Aim. To evaluate the association of Family History (FH) of cardiovascular diseases (CVD) in boys aged 12-13 years with the development of structural and functional changes in the left ventricle and stiffness of the main arteries in adulthood (43-46 years old) according to prospective study.Material and methods. For the initial examination, boys were selected whose parents suffered from CVD at a young age or died prematurely from them (risk group). The comparison group was formed from a population sample of boys of a similar age without FH of CVD. The examination included a survey on a standard questionnaire, measurement of anthropometric indicators, blood pressure (BP), pulse counting, determination of the blood lipid spectrum. The intima-media complex thickness (IMT) of the common carotid arteries was measured; echocardiography and applanation tonometry were performed.Results. The group with FH of CVD significantly (p<0.05) differed in childhood in terms of the body mass index (BMI) (18.8 vs 17.6 kg/m2), systolic BP (SBP) (117 vs 107 mm Hg), diastolic BP (DBP) (67 vs 56 mm Hg), average BP (81.8 vs 72.7 mm Hg) and triglycerides (0.79 vs 0.58 mmol/L). In adulthood, increased total cholesterol (TC) level (6.3 vs 5.8 mmol/L; p=0.036) and other indicators of atherogenesis were revealed in the risk group. The risk of fatal outcomes from CVD in the next 10 years in men with a family history of CVD in childhood was significantly higher compared to the control group (1.94 vs. 1.28; p <0.001). The main contribution to the total risk of fatal CVD in middle-aged men was made by TC and smoking. In the group with FH of CVD, higher stiffness of the arteries in adulthood was observed. There were found significant (p=0.002) intergroup differences in the IMT (0.73 vs 0.63 mm). A statistically significant positive relationship between BMI and some structural and functional indicators of the left ventricle and stiffness indicators of the main arteries was revealed. DBP and mean BP in childhood are associated with arterial stiffness in adulthood according to the parameters of central SBP and central DBP. BMI in boys is the most significant predictor for most structural and functional indicators of LV myocardial hypertrophy, in particular, LV myocardial mass (private R2=0.140) and interventricular septum thickness (R2=0.164; p=0.001), and arterial stiffness by central DBP parameter (R2=0.043; p=0.024) in adulthood. The risk of increased IMT development in males in adulthood with FH of CVD is 6.1 times higher than that of their peers without FH.Conclusion. FH of CVD revealed in childhood in males is a risk factor for the development of early atherosclerosis and, due to its ease of detection, can be used as one of the criteria for the formation of high-risk groups for the purpose of primary prevention.

Epilepsy and vascular risk

Epidemiological studies have shown that mortality increases in patients with epilepsy compared to the general population, and this has been associated with an increased risk of cardiovascular or cerebrovascular events. The role played by classic and more speculative vascular risk factors (e.g. oxidative stress) in the development of vascular disease in these subjects has not yet been clearly established. In this context, antiepileptic drugs (AEDs) may have a differential influence on the vascular risk of patients with epilepsy, as enzyme inducers have been linked to the development of early atherosclerosis. The role of AEDs in the pathogenesis of atherosclerosis is not fully understood, but there are several plausible explanations: they can condition an unfavourable lipid profile, they can increase levels of C-reactive protein and homocysteinaemia, as well as clotting factors, and they can increase oxidative stress. Prolonged use of AEDs can be associated with a wide range of chronic adverse effects, and may also play a key role in the pathogenesis of atherosclerosis in patients with epilepsy. Neurologists and epileptologists who prescribe AEDs should be aware of the potentially unfavourable effects, especially in patients at high risk of vascular events. This review examines the pathophysiological mechanisms that may explain increased vascular risk in epilepsy, the evidence regarding accelerated atherosclerosis and its complications, and the potential implications for follow-up and treatment of the disease.

Особенности цитокинового баланса у больных остеоартрозом и атеросклерозом

The aim of the research is to study the content of some key pro / anti-inflammatory cytokines in patients with osteoarthritis and to evaluate their role in predicting atherogenesis in this category of patients. Material and methods. Patients with primary osteoarthritis of I-III radiological stages were examined. Doppler vessels ultrasound (Doppler ultrasound) of the neck, upper and lower extremities was performed; blood levels of pro / anti-inflammatory cytokines were examined: IL-1β, TNF-α, IL-6, IL- 8, IL-18, MCP-1, IL-17, IL-10, IL-33 by flow cytometry. Results. According to the thickness of intima - media complex, the patients were divided into 2 groups: with a normal thickness of intima - media complex and with atherosclerotic plaque. A significant increase in pro-inflammatory cytokines was revealed in patients with osteoarthritis associated with atherosclerosis compared with those having osteoarthritis with normal thickness of intima-media complex. The level of pro / anti-inflammatory cytokines along with atherosclerosis are closely interconnected. Conclusion. According to the results of the studies obtained, it was found that a long-term subclinical inflammatory process leads to multidirectional disturbances in cytokine balance in patients with osteoarthritis, which probably contributes to the progression of both osteoarthritis and atherosclerosis. A possible factor of early atherosclerosis development in patients with osteoarthritis was also identified.

The Role of Traditional Risk Factors and Inflammation Activity in Atherosclerosis Development in Psoriatic Arthritis Patients

It is known that patients with autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus) have early atherosclerosis development which might lead to the life threatening complications and death. Epidemiology studies demonstrated the risk of myocardial infarction, cardiovascular death is increased in patients with psoriatic arthritis (PsA), which also can be explained by premature atherosclerosis development but its risk factors (RF) remain unclear.The objective: defining relationship of traditional RF for cardiovascular diseases (CVD) with the activity of the inflammatory process and atherosclerosis in patients with PsA.Materials and methods. The study included 42 patients with PsA and 20 patients with skin psoriasis (PS) who did not have atherosclerotic CVD, diabetes, chronic kidney disease and other serious diseases and did not take statins. The control group consisted of 20 healthy persons who had no signs of rheumatic, infectious and other inflammatory diseases. All enrolled patients underwent complete physical examinations, evaluation of disease activity (DAS28, PASI indexes); laboratory investigations included full blood count and ESR, CRP, plasma lipids and uric acid level. Ultrasound of carotid arteries was performed to evaluate the surrogate atherosclerosis markers – intima-media complex thickness (IMT) and atherosclerotic plaques (AP).Results. It was determined that in patients with PsA, the severity of the atherosclerotic process is more prominent compared to patients with PS (the traditional RF profiles were the same).Сonclusion. The highest level of C-reactive protein, fibrinogen, uric acid, thicker intima-media complex was found in PsA group, which may indicate a pathogenetic association of additional RF with the development of a more aggressive atherosclerotic process.

P4450Atherosclerosis in women with systemic lupus erythematosus with and without nephritis

Abstract Background Nephritis in systemic lupus erythematosus (SLE) is a factor contributing to early development of atherosclerosis (AS). Objectives The aim of the study is to determine differences in cardiovascular risk factors and AS in SLE pts with and without lupus nephritis (LN). Methods The study included 162 females, age 35 [26–43] years (median [interquartile range 25–75%])) with SLE (ACR,1997). We divided SLE pts on two groups, comparable in age: the 1st group is the pts with LN (n=84, 52%), the 2nd - without LN (n=78, 48%). We considered traditional factors of cardiovascular disease (CVD): (smoking, family history of CVD, blood pressure, cholesterol (total, HDL, LDL) and triglyceride (TG) levels, body mass index, diabetes mellitus) and SLE-related factors (age at onset, duration, clinical features, SLE Disease Activity Index (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics damage index (SLICC/DI), treatment with steroids); intima-media thickness (IMT) and the 10-year risk for coronary events. Carotid intima-media wall thickness of common carotid arteries was measured by high resolution B-mode ultrasound. The 10-year risk for coronary events was estimated by the Framingham risk equation. Results Median SLE duration was 8,0 [2,3–17,0] years, SLEDAI 2K – 8 [3–16], SLICC/DI score – 2 [0–3], duration of prednisone treatment – 72 [26–141] months. SLE pts from the 1st group had higher prevalence of hypertension (61% vs 36%, p<0,01), systolic blood pressure (130 [110–150] vs 120 [110–130]mm Hg, p<0,01), diastolic blood pressure (80 [70–95] vs 70 [70–80] mm Hg, p<0,05), TG concentration (136 [98–184] vs 100 [61–162] mg/dl, p<0,01), Framingham Risk Score (5 [1–30] vs 1 [1–27]%, p<0,05), SLEDAI-2K (12 [5–19] vs 4 [2–10], p<0,ehz745.08501), SLICC/DI score (2 [0–4] vs 0 [0–2], p<0,01), prednisone therapy duration (95 [26–192] vs 44 [14–98] months, p<0,05), prednisone cumulative dose (34,4 [13,6–82,5] vs 15,7 [6,2–35,2] g, p<0,001), mean IMT (0,73 [0,65–0,83] vs 0,67 [0,61–0,75] mm, p<0,01), than the pts from the 2nd group. There is no difference in CVD frequency in these groups (17% vs 8%, p=0,084). Conclusions SLE patients with and without LN had no difference in frequency of clinical manifestations of AS (CVD), but had a greater value of mean IMT, Framingham Risk Score and a higher incidence of both traditional (hypertension, TG concentration) and SLE-related (disease activity, prednisone therapy) risk factors for AS.

Antisense Oligonucleotide Inhibition of MicroRNA-494 Halts Atherosclerotic Plaque Progression and Promotes Plaque Stabilization

We have previously shown that third-generation antisense (3GA) inhibition of 14q32 microRNA (miRNA)-494 reduced early development of atherosclerosis. However, patients at risk of atherosclerotic complications generally present with advanced and unstable lesions. Here, we administered 3GAs against 14q32 miRNA-494 (3GA-494), miRNA-329 (3GA-329), or a control (3GA-ctrl) to mice with advanced atherosclerosis. Atherosclerotic plaque formation in LDLr−/− mice was induced by a 10-week high-fat diet and simultaneous carotid artery collar placement. Parallel to 3GA-treatment, hyperlipidemia was normalized by a diet switch to regular chow for an additional 5 weeks. We show that, even though plasma cholesterol levels were normalized after diet switch, carotid artery plaque progression continued in 3GA-ctrl mice. However, treatment with 3GA-494 and, in part, 3GA-329 halted plaque progression. Furthermore, in the aortic root, intra-plaque collagen content was increased in 3GA-494 mice, accompanied by a reduction in the intra-plaque macrophage content. Pro-atherogenic cells in the circulation, including inflammatory Ly6Chi monocytes, neutrophils, and blood platelets, were decreased upon miRNA-329 and miRNA-494 inhibition. Taken together, treatment with 3GA-494, and in part with 3GA-329, halts atherosclerotic plaque progression and promotes stabilization of advanced lesions, which is highly relevant for human atherosclerosis.

Chronological in vivo imaging reveals endothelial inflammation prior to neutrophils accumulation and lipid deposition in HCD-fed zebrafish

Background and aimsHyperlipidemia-induced atherosclerosis is the major cause of heart attack and stroke in humans. However, pathological details and molecular mechanisms underlying early atherogenesis remain incompletely characterized. This study explored the early events of atherogenesis in a hypercholesterolemic zebrafish model in vivo. MethodsWe used transparent transgenic zebrafish larvae Tg(lysc:EGFP), Tg(mpx:EGFP), Tg(mpeg1:EGFP), Tg(flk1:EGFP) or Tg(lysc:EGFP/flk1:mCherry), together with fluorescently labeled control and high cholesterol diets (HCD), to dynamically investigate the early development of atherosclerosis with confocal in vivo. Endothelial cells with green fluorescence were sorted by fluorescence-activated cell sorting (FACS) to detect gene expression. Moreover, we treated hypercholesterolemic zebrafish model in vivo or human umbilical vein endothelial cells (HUVEC) in vitro with rosiglitazone, an agonist of peroxisome proliferator-activated receptor γ (PPARγ). ResultsWe found that HCD-induced endothelial inflammation was an earlier pathological alteration than myeloid cells/neutrophils accumulation and lipid deposition in zebrafish vascular vessels of HCD-fed zebrafish. Endothelial inflammation was characterized by down-regulation of anti-inflammatory PPARγ and upregulation of pro-inflammatory tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β). Pharmacological treatment with rosiglitazone reversed the decrease in the expression of PPARγ and decreased expression of TNF-α and IL-1β in HCD-fed zebrafish. Moreover, rosiglitazone ameliorated myeloid cells accumulation and lipid deposition in HCD-fed zebrafish in vivo. ConclusionsHyperlipidemia-induced endothelial inflammation happens earlier than myeloid cell neutrophils accumulation in vascular vessels, and neutrophils accumulation is prior to lipid deposition during the initial stage of atherosclerosis. Early alleviation of inflammation induced by HCD would have a prophylactic effect for the initial development of atherosclerosis.

The latency period between type 2 diabetes and development of Coronary Artery Disease based on psychological factors

ObjectivesDiabetic patients are highly prone to cardiovascular complications. The purpose of this study was to investigate the latency period/time interval between the development of type 2 diabetes and the development of Coronary Artery Disease (CAD) based on psychological factors after adjusting for medical and demographic factors. MethodsThis cross-sectional study was carried out on 264 CAD patients who were suffering also from diabetes mellitus (DM). Patients were divided into three groups based on the duration of their diabetes. Data were collected using a checklist of demographic and medical factors, as well as psychological standard scales. The data were analyzed using a chi-square test, ANOVA and multinomial logistic regression. Results45.5% of the patients developed CAD in less than 5 years; 23.5% in 5–10 years, and 22% more than 10 years after being diagnosed with DM. After adjustment for medical and demographic variables, anxiety (p = 0.003), stressful life events (P = 0.009) and exercise (p = 0.033) were associated with early development of CAD and self-care variables including checking blood sugar (p = 0.001) and taking medication (p = 0.049), lifestyle variables including nutrition (p = 0.003), and perceived physiological risk factors for heart disease (p = 0.002) were inversely associated with early development of CAD. ConclusionsPatients with DM are prone to the early development of CAD, and psychological factors were associated with early development of CAD. Therefore, the findings of the current study can be utilized in designing preventive and therapeutic interventions, and implementing and integrating these factors in health-promotion programs for patients with DM can be useful.

Liraglutide Attenuates Preestablished Atherosclerosis in Apolipoprotein E-Deficient Mice via Regulation of Immune Cell Phenotypes and Proinflammatory Mediators.

We have shown that the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide (Lir) inhibits development of early atherosclerosis in vivo by modulating immune cell function. We hypothesized that Lir could attenuate pre-established disease by modulating monocyte or macrophage phenotype to induce atheroprotective responses. Human atherosclerotic plaques obtained postendarterectomy and human peripheral blood macrophages were treated ex vivo with Lir. In parallel, apolipoprotein E-deficient (ApoE-/-) mice received a high-fat, high-cholesterol diet to induce atherosclerosis for 8 weeks, after which ApoE-/- mice received 300 μg/kg of Lir daily or vehicle control for a further 4 weeks to investigate the attenuation of atherosclerosis. Lir inhibited proinflammatory monocyte chemoattractant protein-1 secretion from human endarterectomy samples and monocyte chemoattractant protein-1, tumor necrosis factor-α, and interleukin (IL)-1β secretion from human macrophages after ex vivo treatment. An increase in CD206 mRNA and IL-10 secretion was also detected, which implies resolution of inflammation. Importantly, Lir significantly attenuated pre-established atherosclerosis in ApoE-/- mice in the whole aorta and aortic root. Proteomic analysis of ApoE-/- bone marrow cells showed that Lir upregulated the proinflammatory cathepsin protein family, which was abolished in differentiated macrophages. In addition, flow cytometry analysis of bone marrow cells induced a shift toward reduced proinflammatory and increased anti-inflammatory macrophages. We concluded that Lir attenuates pre-established atherosclerosis in vivo by altering proinflammatory mediators. This is the first study to describe a mechanism through which Lir attenuates atherosclerosis by increasing bone marrow proinflammatory protein expression, which is lost in differentiated bone marrow-derived macrophages. This study contributes to our understanding of the anti-inflammatory and cardioprotective role of GLP-1RAs. SIGNIFICANCE STATEMENT: It is critical to understand the mechanisms through which liraglutide (Lir) mediates a cardioprotective effect as many type 2 diabetic medications increase the risk of myocardial infarction and stroke. We have identified that Lir reduces proinflammatory immune cell populations and mediators from plaque-burdened murine aortas in vivo and augments proresolving bone marrow-derived macrophages in attenuation of atherosclerotic disease, which provides further insight into the atheroprotective effect of Lir.

MARKERS OF VASCULAR DAMAGE IN CHILDREN AND ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS

Objective: Type 1 diabetes mellitus (T1DM) is associated with early development of atherosclerosis. The aim of this study was to measure some indices of vascular damage in a group of children and adolescents with T1DM and their relationship with haemodynamic and metabolic parameters. Design and method: In a cross-sectional study, peripheral (pSBP/pDBP) and central systolic and diastolic blood pressure (cSBP/cDPB), carotid intima media thickness (cIMT) and carotid distensibility (cDC), pulse wave velocity (PWV) were measured using ultrasound and the SphygmoCor XCel device. Metabolic parameters, including triglycerides, LDL and HDL-cholesterol, were measured and glycated haemoglobin (HbA1c; average of the last two years) was calculated. Results: 126 subjects with T1DM (61 females and 65 males, mean age 15.9 ± 2.6 years) followed at the Paediatric Diabetology Unit of Verona were evaluated at the Vascular Laboratory of the General Medicine & Hypertension Unit. Eighteen per cent of the sample had cDC under the 5th percentiles and 60% had cIMT higher than the 95th percentiles per sex and height. Both cSBP and pSBP were positively correlated with BMI (respectively r = 0.404; p < 0.0001 and r = 0.279; p < 0.01). A significant correlation between cSBP and all the measures of vascular damage was found: cDC (r = −0.410; p < 0.0001), PWV (r = 0.447; p < 0.0001), cIMT (r = 0.227; p < 0.01). The duration of diabetes, LDL-cholesterol and the average HbA1c were not correlated to any vascular phenotype. In linear regression analysis, after adjustment for all metabolic and anthropometric parameters, central SBP remained independently associated with subclinical carotid damage (for cIMT β = 0.002; p = 0.023; for cDC β = −0.343; p = 0.003) and PWV (β = 0.025; p < 0.001) whereas LDL-cholesterol with cIMT (β = 0.001; p < 0.05) and PWV (β = 0.025; p < 0.01). Conclusions: Subclinical vascular damages are present in a high proportion of children and adolescents with T1DM. cSBP, more than pBP, is independently associated with indexes of vascular subclinical atherosclerosis, suggesting a pivotal role of blood pressure homeostasis, along with LDL-cholesterol, in determining vascular damage even during childhood and adolescence in patients with T1DM.

Pediococcus acidilactici AS185 attenuates early atherosclerosis development through inhibition of lipid regulation and inflammation in rats

Abstract Pathophysiologic mechanisms underlying atherosclerosis (AS) development are linked to dyslipidemia and inflammation. Pediococcus acidilactici AS185, a probiotic, was isolated from traditional farmers’ soybean paste (Yanji, China). This study aimed to assess P. acidilactici AS185 anti-atherosclerotic effects and elucidate molecular mechanisms of action using an early AS model of SD rats fed a high-fat diet with intraperitoneal vitamin D3 (VD3) injections. For 8 weeks, model rats received P. acidilactici AS185 via gavage once/day. Post-treatment serum levels of inflammatory mediators, lipids, adhesion molecules, aortic histopathological characteristics and AS-related aortic protein expression levels were assessed. P. acidilactici AS185 administration markedly increased serum HDL-C and IL-10 levels, while reducing serum TG, LDL-C, TC, Ox-LDL, ICAM-1, VCAM-1, TNF-α, IFN-γ, IL-1β, and IL-6 levels. Notably, P. acidilactici AS185 inhibited p-p38 and ERK1/2 MAPK pathways and decreased Ox-LDL and CD36 expression to attenuate early AS by altering lipid profiles and MAPK-signaling-based inflammation.

Endocrine and metabolic consequences of surgical interventions in uterine myoma: pathogenetic characteristic

This paper presents analysis results of the research on endocrine and metabolic disorders in women who underwent surgery interventions for uterine myomas. Uterine myoma is one of the most common gynecological diseases. Main types of surgical interventions to treat uterine myomas are: hysterectomy, which is an organ-removing operation with various volume of surgical intervention: supravaginal amputation or extirpation of the uterus. Another type is myomectomy — an organ-preserving operation — when myoma nodes are removed, but the uterus and ovaries are preserved if they have no pathology. Removal of the uterus with appendages or without ovaries results in a decreasing production of estrogens, which play a key role in regulation of metabolism and various functions of the body systems. Estrogen deficiency, occurring after hysterectomy, deprives patients of a comprehensive protective effect of female sex hormones in all types of metabolism and normal functioning of organ systems. Hypoestrogenemia leads to development of a post-hysterectomy syndrome that comes out in early development of atherosclerosis, circulatory diseases, osteoporosis, psychological status disorders and urogenital disorders. Hypoestrogenemia is a key link in the pathogenesis of endocrine and metabolic disorders after hysterectomy. Endocrine disorders can be found at almost all levels of the regulatory and executive axis of the endocrine system. So far, hormonal function of the peripheral endocrine glands after myomectomy has been poorly studied. Currently available publications give no data on endocrine and metabolic disorders in patients after the myomectomy.

Protective Effects of Angong Niuhuang Pill on Early Atherosclerosis in ApoE-/- Mice by Reducing the Inflammatory Response.

Atherosclerosis (AS) is the primary cause of cardiocerebrovascular disease, and inflammation is responsible for the initiation of its pathogenesis. Therefore, targeting inflammatory pathways to prevent AS progression is an ideal strategy. Angong Niuhuang pill (ANP) is a well-known traditional Chinese medicine and has been widely used for thousands of years to treat central nervous system and cardiovascular diseases. In this study, we investigated the role of ANP in reducing inflammation during early AS, using a high-fat diet-induced ApoE−/− mouse model of AS. Compared to those with simvastatin, ANP had no significant effect on serum triglyceride, low-density lipoprotein, and high-density lipoprotein levels. However, it effectively inhibited splenic and vascular inflammation. This agent also reduced the Th17/CD4+T ratio and mRNA expression of IL-6 and increased the Treg/CD4+T ratio and mRNA expression of TGF-β1. Thus, ANP restored Th17/Treg homeostasis in the spleen. It also regulated pro- and anti-inflammatory cytokine expression in the aorta in a similar manner. Further, it downregulated the expression of chemokine receptors (CCR2, CXCR3), their ligands (MCP-1, MCP-2, and MCP-3), and cell adhesion molecules (VCAM-1, ICAM-1) in arterial vessels. These results indicate that ANP can ameliorate the development of early AS, mainly by reducing inflammation instead of acting as an antihyperlipidemic drug.

Effect of uric acid serum levels on carotid arterial stiffness and intima-media thickness: A high resolution Echo-Tracking Study.

Serum uric acid (UA) has been shown to be a predictor of cardiovascular (CV) morbidity and mortality, and it may play a role in the pathogenesis of CV disease affecting vascular structure and function. However, there is limited evidence of its specific association with carotid artery stiffness and structure. The aim of our study was to evaluate whether UA is associated with early signs of atherosclerosis, namely local carotid arterial stiffness and intima-media thickening. We evaluated 698 consecutive asymptomatic patients, referred to the Cardiovascular Department for risk factors evaluation and treatment. All patients underwent carotid artery ultrasonography with measurement of common carotid intima-media thickness (IMT) and echo-tracking carotid artery stiffness index Beta. Patients with hyperuricemia (defined as serum uric acid ≥7 mg/dL in men and ≥6 mg/dL in women) had higher IMT (0.97±0.22 vs 0.91±0.18, p<0.001) and stiffness index Beta (8.3±3.2 vs 7.5±2.7, p=0.005). UA levels correlated with both IMT (r=0.225; p<0.001) and stiffness index Beta (r=0.154; p<0.001); the correlations were statistically significant in males and females. In a multivariate model which included age, arterial pressure, serum glucose and LDL-cholesterol, serum UA emerged as an independent explanatory variable of IMT and stiffness index Beta. Carotid IMT and local arterial stiffness are related to UA independently of established CV risk factors; UA may play a role in the early development of atherosclerosis.