Cola Beverages Accelerate Growth of the Atherosclerotic Plaque in ApoE-/- Mice

Introducción: Los hábitos de alimentación poco saludables durante la infancia y la juventud se han suge­rido como favorecedores de las complicaciones ateroscleróticas en edades más avanzadas. El creciente consumo de bebidas cola en las últimas décadas se ha asociado con el desarrollo de obesidad e incremento en la incidencia de aterosclerosis y enfermedades cardiovasculares. A su vez, se sabe que existe correspondencia entre el consumo de estas bebidas y etapas de la vida, el cual es mayor en los niños, los adolescentes y los adultos jóvenes. Objetivo: Evaluar el efecto del consumo de bebidas cola sobre la aterosclerosis. Material y métodos: Se distribuyeron ratones ApoE-/- (8 semanas de edad) en tres grupos según el consumo libre de agua (A), bebida cola azucarada (C) y bebida cola edulcorada light (L). Al cabo de 8 semanas las bebidas cola se reemplazaron por agua. Los ratones fueron sacrificados secuencialmente: antes del tratamiento (8 semanas de edad) y luego de su interrupción (16, 20, 24 y 30 semanas de edad). Se extrajeron la aorta ascendente y el hígado. Se calculó la relación entre el área de la placa aórtica y el espesor de la capa media (relación placa/media). Se evaluó la inflamación del parénquima hepático según la escala de NASH. Resultados: La relación placa/media varió según la bebida (F2,54 = 3,433, p < 0,04) y la edad (F4,54 = 5,009, p < 0,03) y fue mayor en los grupos C y L (p < 0,05 a las 16 y 20 semanas, p < 0,01 a las 24 y 30 semanas). La inflamación del parénquima hepático (F2,9 = 13,29, p < 0,002) y portal (F2,9 = 6,30, p < 0,02) aumentó cinco y dos veces, respectivamente, en función del tiempo (p < 0,01 y p < 0,03) entre las semanas 20 y 30, en contraste con la esteatosis y el daño hepatocelular, que no se modificaron. El grupo A (evolución natural de la aterosclerosis) se caracterizó por la aceleración del crecimiento del área de placa en paralelo con un rápido aumento de la inflamación hepática alrededor de la semana 20. Conclusiones: El consumo de bebidas cola en ratones ApoE-/- entre las semanas 8 y 16 de edad aumentó la tasa de progresión de la aterosclerosis. Los datos sugieren que, en este modelo murino, el consumo sostenido de bebidas cola durante las etapas tempranas de la vida puede acelerar el agravamiento del daño aterosclerótico en etapas más tardíasIntroduction: Unhealthy eating habits during childhood and youth have been suggested as predisposing factors to atherosclerotic complications later in life. The growing consumption of cola beverages in recent decades has been associated with the development of obesity and increased incidence of atherosclerosis and cardiovascular disease. We also know that there is a correspondence between the consumption of these beverages and the different stages of life, being higher in children, adolescents and young adults. Objective: This study evaluates the effect of cola beverage consumption on atherosclerosis. Methods: ApoE-/- mice (8 week-old) were randomized into 3 groups according to free access to water (W), sucrose sweetened carbonated cola drink (C) or aspartame-acesulfame K sweetened carbonated ‘light' cola drink (L). At 8 weeks cola beverages were switched to water. The mice were sequentially euthanized: before treatment (8 week old mice) and after treatment discontinuation (20, 24, and 30 week old mice). The ascending aorta and the liver were removed. Aortic plaque area was analyzed and plaque/media-ratio was calculated. Hepatic inflammation was assessed according to the NASH scale. Results: Plaque/media-ratio varied according to drink treatment (F2,54=3.433, p <0.04) and age (F4,54=5.009, p <0.03) and was higher in the C and L groups (p <0.05 at 16 and 20 weeks, p <0.01 at 24 and 30 weeks). Hepatic parenchymal inflammation (F2,9=13.29, p <0.002) and portal inflammation (F2,9 =6.30, p <0.02) varied fivefold and twofold in contrast to steatosis and hepatocellular damage which remained unchanged throughout the study.Natural evolution of atherosclerosis in ApoE-/- mice (W group) evidenced acceleration of plaque growth in parallel with a rapid increase in hepatic inflammation around week 20 of age. Conclusions: Cola beverage consumption in 8-16 week old ApoE-/- mice accelerated atherosclerosis progression. Data suggest that, in this murine model, sustained cola consumption at early stages of life may predispose to atherosclerosis progression later in life.Fil: Serafini, Enriqueta M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Otero Losada, Matilde E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Rodriguez Granillo, Gaston Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Aguilera, Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Muller, Angelica del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Ottaviano, Graciela Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Azzato, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Milei, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); Argentin

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Carvedilol protects the peritubular capillaries and kidney structure in spontaneously hypertensive rats

Carvedilol improves autoregulation of renal blood flow by virtue of its ability to reduce intrarenal vascular resistance [1] and modify the vascular reactivity in non-denervated kidney [2]. Long-term changes in renal blood flow, for example during essential hypertension, may induce progressive modifications in the microvascular (MV) tone, given that the chronic vascular constriction can lead to peritubular capillary loss and increased intrarenal vascular resistance. The severity of these changes may affect the kidney functions, a phenomenon known as vascular rarefaction [3].Fil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Milei, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Muller, Angelica del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Ottaviano, Graciela Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Gómez Llambí, Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); Argentin

Rosuvastatin increases myocardial microvessels in SHR rats. Role of thioredoxin-1 and peroxiredoxin-2 expression

Beyond their lipid-lowering action, rosuvastatin possesses pleiotropic effects including anti-inflammatory, pro-angiogenic, antioxidant effects and protective actions against endothelial dysfunction [1,2]. The spontaneously hypertensive rats (SHR) have been extensively studied as a model of essential hypertension. Analogous to that seen in humans, prolonged periods of hypertension produce left ventricular (LV) remodeling, hypertrophy and oxidative stress. Thioredoxin (Trx) and peroxiredoxin (Prx) are a ubiquitous family of cysteine-dependent antioxidant proteins, present in mammalian cells including the heart. Several reports exist in the literature indicating that these proteins are induced by oxidative stress [3]. We investigated the possible effect of long-term monotherapy with rosuvastatin in myocardial expression of redoxins and vascular endothelial growth factor (VEGF), and their relations with LV remodeling in adult SHR. Eight-week-old male SHR and Wistar-Kyoto (WKY) rats, were divided into three groups: SHR (n = 20), SHR-R (n = 20; rosuvastatin 10 mg/kg/day) and WKY (n = 20).Fil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Gómez Llambí de Oromí, Hernán Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Muller, Angelica del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Ottaviano, Graciela Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentin

Altered elimination of organic anions in rats with chornic renal failure

The progress of chronic renal failure (CRF) is characterized by the development of glomerular and tubular lesions. However, little is known about the expression of organic anions renal transporters. The objective of this work was to study, in rats with experimental CRF (5/6 nephrectomy), the expression of the organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) and their contribution to the pharmacokinetics and renal excretion of p-aminohippurate (PAH). Two groups of animals were used: Sham and CRF. Six months after surgery, systolic blood pressure and plasma creatinine concentrations were significantly higher in CRF groups. CRF rats showed a diminution in: the filtered, secreted and excreted load of PAH; the systemic clearance of PAH; the renal OAT1 expression; and the renal Na-K-ATPase activity. No remarkable modifications were observed in the OAT3 expression from CRF kidneys. The diminution in the systemic depuration and renal excretion of PAH may be explained by the decrease in its filtered and secreted load. The lower OAT1 expression in remnant renal mass of CRF rats or/and the lower activity of Na-K-ATPase might justify, at least in part, the diminished secreted load of this organic anion.Fil: Torres, Adriana Mónica. Universidad Nacional de Rosario; ArgentinaFil: Mac Laughlin, Myriam Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Muller, Angelica del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Brandoni, Anabel. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Anzai, Naohiko. Kyorin University; JapónFil: Endou, Hitoshi. Kyorin University; Japó

Transforming Growth Factor b1 and Coronary Intimal Hyperplasia in Pediatric Patients With Congenital Heart Disease

Background Congenital heart defects or the process of their repair leads to an increased risk for adult cardiovascular disease compared with the general population. Intimal hyperplasia is a preatherosclerotic lesion that may be produced as a consequence of transforming growth factor β1 (TGF-β1) pathway activation. We studied the presence of intimal hyperplasia in arteries from a pediatric population with congenital heart disease (CHD) and TGF-β1 expression to enlighten its possible role in the genesis of these lesions. Methods Coronary arteries from 10 controls and 98 CHD patients (54% cyanotic type, 32% surgically repaired) were stained, and the presence and degree of intimal thickening were analyzed. The expression of TGF-β1 was studied by immunohistochemistry. Results The difference between the presence of coronary intimal hyperplasia in patients with cyanotic (35; 66.1%) and noncyanotic CHD (29; 64.3%) was not significant. However, surgically repaired CHD presented a higher rate of coronary intimal hyperplasia (80%) than did the group without surgical intervention (47.3%), P = 0.0002. The immunostaining for TGF-β1 analyzed in samples of patients with cyanotic and noncyanotic CHD showed no significant differences. However, TGF-β1 expression was more intense on the intimal layer of patients with surgically repaired CHD than on that of those without surgery (intimal area positive for TGF-β1, 50.43% vs 15.91%, respectively; Mann-Whitney U test P = 0.0005). Conclusion The high incidence of intimal hyperplasia in patients with surgically repaired CHD is correlated with TGF-β1 expression and may contribute to the development of atherosclerotic coronary artery disease in CHD patients.Fil: Guerri Guttenberg, Roberto Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Castilla, Rocío. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Francos, Gabriela C.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutierrez"; ArgentinaFil: Muller, Angelica del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Ambrosio, Giuseppe. Universita Di Perugia; ItaliaFil: Milei, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); Argentin

Inverse expression of estrogen receptor alpha and apolipoprotein B in coronary intimal hyperplasia of surgically repaired congenital heart disease: A pre-atherosclerotic condition?

Congenital heart diseases (CHD) or the process of their repair leads to an increased risk for adult cardiovascular disease compared with the general population. The proliferation of intimal smooth muscle cells (SMCs), which causes intimal thickenings prior to any evidence of visible lipid deposition, was proposed to be the initial lesion of coronary atherosclerosis. The increasing trend to consider intimal thickenings as possible pre-atherosclerotic lesions is based on the distribution of intimal hyperplasia in children and the localization of characteristic atherosclerotic lesions observed in adult humans. Early coronary artery lesions may range from focal areas with mild myointimal thickenings in prenatal life to early soft plaques in infants, which may also present as intermingled lesions with components of both categories, more frequently observed with increasing age. Also,we proposed that TGF-β1 expressionmight be considered another possible predisposing factor to develop atherosclerotic coronary artery disease in CHD patients. On the other hand, estrogen receptor-α (ERα) appears to be responsible for the protective effects of estrogens against atherosclerotic vascular disease. The aim of this paper was to analyze the immunohistochemical expression of ERα, TGF-β1 and apolipoprotein B in coronary intimal hyperplasia in children with CHD and the possible increased risk for the development pre-atherosclerotic lesions.Fil: Castilla Lozano, Maria del Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Kolliker Frers, Rodolfo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Muller, Angelica del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Ambrosio, Giuseppe. Universita Di Perugia; ItaliaFil: Milei, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); Argentin

Biochemical Changes and Aortic Atherosclerosis in a Colony of Apolipoprotein-E Deficient Mice: A Possible Model?

Aim. To evaluate the sequence of biochemical and pathological changes in liver and abdominal aorta in apolipoprotein-E deficient mice (8 weeks old, standard diet) in relation with age. Materials and methods: euthanasia (pentobarbital sodium and phenytoin) was practiced at 16, 20 and 30 weeks of age. Glycemia and the level of total cholesterol and its fractions were biochemically routinely determined. Sections of the liver and the ascending aorta were dissected and conventionally processed for morphology and morphometry. Results: hyperglycemia was observed at 20 weeks (39%, p<0.02). Hypertriglyceridemia (x2.8, p<0.01), an increase in non-HDL cholesterol (71%, p<0.05) and a decrease in HDL cholesterol (-26%, p<0.05) were found at 30 weeks. Liver inflammation and portal inflammation increased (4-fold, p<0.01 and 2-fold, p<0.03 respectively) between weeks 20-30. At week 30: aortic plaque area and the percentage of stenosis increased (respectively 5-fold, p<0.0001 and 2.4-fold, p<0.01) and the intima-media ratio increased (3-fold, p<0.05) with media thinning (-69 %, p<0.01). Preatherosclerotic lesions consisted of subendothelial clusters of foamy cells in contrast with intimal thickening due to smooth muscle cell proliferation as typically found in man. Conclusion: ApoE-/- mice spontaneously developed early hyperglycemia, followed by dyslipidemia with hypertriglyceridemia, and hepatic and aortic pathology. The sequence of the changes suggests that hypertriglyceridemia, decreased levels of HDL and hepatic inflammation favored aortic damage progression. Otherwise morphologically similar, the sequence of events resulting in plaque formation is different to that found in man. Bearing this in mind, the ApoE-/- mice model may be used to study the biochemical and molecular events underlying atherosclerosis.Fil: Aguilera, Aída J.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Otero-losada, Matilde Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Serafini, Enriqueta M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Muller, Angelica del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Azzato, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Milei, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); Argentin