Evaluation of the participation of ABCA1 transporter in epicardial and mediastinal adipose tissue from patients with coronary artery disease

ABSTRACT Objective: Recent studies have shown a relationship between adipose tissue and coronary artery disease (CAD). The ABCA1 transporter regulates cellular cholesterol content and reverses cholesterol transport. The aim of this study was to determine the relationship between single nucleotide polymorphisms (SNPs) R230C, C-17G, and C-69T and their expression in epicardial and mediastinal adipose tissue in Mexican patients with CAD. Subjects and methods: The study included 71 patients with CAD and a control group consisting of 64 patients who underwent heart valve replacement. SNPs were determined using TaqMan probes. mRNA was extracted using TriPure Isolation from epicardial and mediastinal adipose tissue. Quantification and expression analyses were done using RT-qPCR. Results: R230C showed a higher frequency of the GG genotype in the CAD group (70.4%) than the control group (57.8%) [OR 0.34, 95% CI (0.14-0.82) p = 0.014]. Similarly, C-17G (rs2740483) showed a statistically significant difference in the CC genotype in the CAD group (63.3%) in comparison to the controls (28.1%) [OR 4.42, 95% CI (2.13-9.16), p = 0.001]. mRNA expression in SNP R230C showed statistically significant overexpression in the AA genotype compared to the GG genotype in CAD patients [11.01 (4.31-15.24) vs. 3.86 (2.47-12.50), p = 0.015]. Conclusion: The results suggest that the GG genotype of R230C and CC genotype of C-17G are strongly associated with the development of CAD in Mexican patients. In addition, under-expression of mRNA in the GG genotype in R230C is associated with patients undergoing revascularization.

Expressions of mRNA and encoded proteins of mitochondrial uncoupling protein genes (UCP1, UCP2, and UCP3) in epicardial and mediastinal adipose tissue and associations with coronary artery disease

ABSTRACT Objective: To evaluate the expression of UCP1, UCP2, and UCP3 mRNA and encoded proteins in epicardial and mediastinal adipose tissues in patients with coronary artery disease (CAD). Subjects and methods: We studied 60 patients with CAD and 106 patients undergoing valve replacement surgery (controls). Expression levels of UCP1, UCP2, and UCP3 mRNA and encoded proteins were measured by quantitative real-time PCR and Western blot analysis, respectively. Results: We found increased UCP1, UCP2, and UCP3 mRNA levels in the epicardial adipose tissue in the CAD versus the control group, and higher UCP1 and UCP3 mRNA expression in the epicardial compared with the mediastinal tissue in the CAD group. There was also increased expression of UCP1 protein in the epicardial tissue and UCP2 protein in the mediastinum tissue in patients with CAD. Finally, UCP1 expression was associated with levels of fasting plasma glucose, and UCP3 expression was associated with levels of high-density lipoprotein cholesterol and low-density cholesterol in the epicardial tissue. Conclusions: Our study supports the hypothesis that higher mRNA expression by UCP genes in the epicardial adipose tissue could be a protective mechanism against the production of reactive oxygen species and may guard the myocardium against damage. Thus, UCP levels are essential to maintain the adaptive phase of cardiac injury in the presence of metabolic disorders.

Expressão de Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade (LRP1) em Monócito em Correlação com EIMC em Pacientes Mexicanos Hipertensos / Monocyte Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Expression Correlates with cIMT in Mexican Hypertensive Patients

Resumo Fundamento A hipertensão arterial (HTA) representa um grande fator de risco de morbidade e mortalidade cardiovascular. Ainda não se sabe que mecanismos moleculares específicos estão associados ao desenvolvimento de hipertensão essencial. Objetivo Neste trabalho, analisamos a associação entre expressão mRNA de monócito LRP1, expressão de proteína LRP1, e espessura íntima-média de carótida (EIMC) de pacientes com hipertensão essencial. Métodos A expressão mRNA de monócito LRP1 e os níveis de proteína e EIMC foram quantificados em 200 indivíduos mexicanos, sendo 91 normotensos (NT) e 109 hipertensos (HT) A significância estatística foi definida em p < 0,05. Resultados O grupo de pacientes HT tinha EIMC maior altamente significativa em comparação com os pacientes NT (p = 0,002), e isso está relacionado ao aumento na expressão mRNA de LRP1 (6,54 versus. 2,87) (p = 0,002) e expressão de proteína LRP1 (17,83 versus 6,25), respectivamente (p = 0,001). Essas diferenças foram mantidas mesmo quando dividimos nossos grupos de estudo, levando em consideração apenas aqueles que apresentavam dislipidemia na expressão de mRNA (p = 0,041) e de proteínas (p < 0,001). Também se identificou que a indução de LRP1 mediada por LRP1 em monócitos em de maneira dependente de dose e tempo, com diferença significativa em NT versus HT (0,195 ± 0,09 versus 0,226 ± 0,12, p = 0,046). Conclusão Foi encontrado um aumento em EIMC em indivíduos com hipertensão, associada a expressões de proteína LRP1 e mRNA mais altas em monócitos, independente da presença de dislipidemia em pacientes HT. Esses resultados que a upregulation de LRP1 em monócitos de pacientes hipertensos mexicanos poderia estar envolvida na diminuição da EIMC. (Arq Bras Cardiol. 2021; 116(1):56-65)

Abstract Background Arterial hypertension (HTA) represents a major risk factor for cardiovascular morbidity and mortality. It is not yet known which specific molecular mechanisms are associated with the development of essential hypertension. Objective In this study, we analyzed the association between LRP1 monocyte mRNA expression, LRP1 protein expression, and carotid intima media thickness (cIMT) of patients with essential hypertension. Methods The LRP1 monocyte mRNA expression and protein levels and cIMT were quantified in 200 Mexican subjects, 91 normotensive (NT) and 109 hypertensive (HT). Statistical significance was defined as p < 0.05. Results HT patients group had highly significant greater cIMT as compared to NT patients (p=0.002) and this correlated with an increase in the expression of LRP1 mRNA expression (6.54 vs. 2.87) (p = 0.002) and LRP1 protein expression (17.83 vs. 6.25), respectively (p = 0.001). These differences were maintained even when we divided our study groups, taking into account only those who presented dyslipidemia in both, mRNA (p = 0.041) and proteins expression (p < 0.001). It was also found that Ang II mediated LRP1 induction on monocytes in a dose and time dependent manner with significant difference in NT vs. HT (0.195 ± 0.09 vs. 0.226 ± 0.12, p = 0.046). Conclusion An increase in cIMT was found in subjects with hypertension, associated with higher mRNA and LRP1 protein expressions in monocytes, irrespective of the presence of dyslipidemias in HT patients. These results suggest that LRP1 upregulation in monocytes from Mexican hypertensive patients could be involved in the increased cIMT. (Arq Bras Cardiol. 2021; 116(1):56-65)

Calidad de vida y perspectiva espiritual de los pacientes hospitalizados con enfermedad cardiovascular / Quality of life and spiritual perspective of hospitalized patients with heart disease

ResumenIntroducción: las cardiopatías son enfermedades crónicas que alteran la calidad de vida de las personas. En este sentido la espiritualidad juega un papel importante, pues a partir de sus creencias y prácticas los pacientes pueden encontrar la fortaleza necesaria para sobrellevar la enfermedad. Objetivo: analizar la calidad de vida y la perspectiva espiritual que tienen los pacientes hospitalizados ante una enfermedad cardiovascular.Metodología: estudio transversal analítico en una muestra aleatoria de 297 pacientes cardiópatas de ambos sexos. Los datos se recolectaron bajo consentimiento informado con el Spiritual Perspective Scale y el WHOQoL-BREF. El análisis estadístico fue descriptivo y se aplicaron pruebas de correlación de Pearson y Spearman, y comparación con t de Student y U de Mann-Whitney para las variables calidad de vida y espiritualidad.Resultados: el 53.5% percibió su calidad de vida como normal y 44.8% como buena; 68% tuvo un nivel alto de espiritualidad. La calidad de vida se relacionó con la espiritualidad (r = 0.164, p = 0.005), especialmente con las creencias (r = 0.214, p = 0.000); el grado académico se asoció con la calidad de vida (rs = -0.288, p = 0.000), pero no con la espiritualidad (rs = -0.030, p = 0.606). La espiritualidad fue mayor en las mujeres (Z = -2.245, p = 0.025).Conclusiones: los pacientes con enfermedad cardiovascular incrementan sus prácticas y creencias espirituales. Esto contribuye en la percepción que tienen sobre su calidad de vida.

AbstractIntroduction: Heart diseases encompass several chronic diseases that can affect the quality of life (QoL) of people. In this sense, spirituality plays an important role, given that by using it patients can find the necessary strength to overcome the disease on the basis of their beliefs and practices. Objective: To analyze the QoL and the spiritual perspective of hospitalized patients facing a heart disease.Methods: Analytical cross-sectional study in a random sample of 297 heart disease patients of both sexes. Data were collected under informed consent with the Spiritual Perspective Scale and the WHOQOL-BREF. The analysis was descriptive. To analyze the variables quality of life and spirituality we used Pearson's correlation coefficient and Spearman's rank correlation coefficient, and we compared them with Student's t test and Mann-Whitney U test.Results: 53.5% perceived their QoL as normal, and 44.8% as good; 68% had a high level of spirituality. The QoL was related to spirituality (r = 0.164, p = 0.005), especially with the beliefs (r = 0.214, p = 0.000); the academic degree was associated with QoL (rs = - 0.288, p = 0.000), but not with spirituality (rs= -0.030, p = 0.606). Spirituality is greater in women (Z = 2.245, p = 0.025). Conclusions: Patients with heart disease increase their practices and spiritual beliefs. This contributes to the perception of their quality of life.

Miocarditis aguda primaria. Experiencia de diez años en el Instituto Nacional de Cardiología "Ignacio Chávez" / Primary Acute Myocarditis. A 10- years institutional experience at the National Institute of Cardiology "I. Chavez"

La miocarditis aguda (MA) se asocia a infecciones virales: Coxsackie B, ECHOvirus y otros. Mecanismos autoinmunes se suponen patogénicos. La clínica es variable. El beneficio de inmunosupresión clásica (prednisona-azatioprina) o inmunomodulación (IgG-monomérica) no ha sido confirmado. Objetivo: Revisar la incidencia y enfoque de estudio de la miocarditis. Material y métodos: De 1992-2003, aplicamos un cuestionario estándar a 49 pacientes consecutivos con diagnóstico establecido en forma independiente. Se excluyeron MA con causa identificable. Resultados: La MA ocurrió en 17 mujeres y 32 hombres, edad (mediana) 24 y 28 años. Predominaron disnea/ortopnea (70-47%), edema/plétora yugular (41-37%), dolor precordial y taquicardia (50%). En 22 (45%) la clase funcional era III-IV. El electrocardiograma mostró taquicardia sinusal (35%) y bloqueos de rama (24%). En 47 pacientes el ecocardiograma mostró FEVI 41% (promedio), DDVI 53 mm (promedio) y discinesia 89%. En 11 (22%) casos investigamos anticuerpos contra Coxsackie/ECHOvirus, 6 (54%) tenían anticuerpo reconocido. Veintinueve casos (61%) progresaron a miocardiopatía dilatada (MD), hubo tres defunciones (6%). No fue posible valorar tratamiento inmunomodulador, se estudió sólo a 12 casos. Conclusiones: La incidencia de MAes 1/1,000 ingresos/año. Es necesario estandarizar manejo diagnóstico y tratamiento, pues la progresión a MD y/o muerte en etapa aguda ocurre en 2/3 de los pacientes.

Acute myocarditis (AM) is associated with viral infections: Coxsackie and ECHOviruses among others. Autoimmunity has been proposed as a pathogenic mechanism. Benefit of classic immunosuppression (prednisone-azathioprine) or immunomodulation (monomeric-human IgG) is still uncertain. Objective: To review incidence and clinical approach to AM at a Cardiology referral center. Material and methods: A 10-yeard period (1992-2003) is reviewed. A standard ques-tionary was applied to 49 consecutive patients referred by clinicians with a diagnosis of AM. Results: AM was found in 17 women and 32 men, median age 24 and 28 years, respectively. They presented heart failure with dyspnea/ortop-nea (70-47%), peripheral edema/jugular vein plethora (41-37%), chest pain, and tachycardia (50%), NYHA functional class was III-IV in 22. The EKG showed sinus tachycardia or conduction defects. Transthoracic echocardiograms in 47 cases showed EF (mean) of 41% with enlarged left ventricle diameter. Antivirus antibodies were present in 54% of those cases studied, Coxsackie or ECHOvirus were identified through a serologic assay. Twenty-nine (61%) of our cases developed dilated cardiomyopathy, three patients died. It is not possible to reach a conclusion regard to immunomodulation therapy, because it was applied to only 12 patients. Conclusions: At the Instituto Nacional de Cardiología "I. Chávez", AM depicts an incidence of 1/1,000 patients a year. It is necessary to standardize the clinical approach for diagnosis and treatment, progression to dilated cardiomyopathy and deadth during acute stage occurs in two-thirds of our patients.

Actividad inflamatoria en arteritis de Takayasu. Detección mediante tomografía por emisión de positrones (PET) / Inflammatory activity in Takayasu arteritis. Detection through positron emission tomography (PET)

La arteritis de Takayasu (AT), es una enfermedad crónica que afecta principalmente a la aorta y sus ramas. Su etiología aún es desconocida, sin embargo se sabe que existe un predominio por el género femenino y que inicia generalmente en los jóvenes. La enfermedad parece tener dos fases, una temprana que se caracteriza por un proceso inflamatorio y otra fase crónica que es caracterizada por oclusión vascular. Hasta ahora el diagnóstico y la clasificación son predominantemente clínicos basados en los criterios del ACR y apoyados por estudios de imagen como la panaortografia o la tomografia computada. Actualmente existen nuevos estudios de diagnóstico por imagen como la resonancia magnética (RM) y la tomografia por emisión de positrones (PET), esta última por su capacidad para valorar el metabolismo podría ser de gran ayuda en el diagnóstico, detección de actividad inflamatoria y seguimiento de los pacientes con AT. Se presenta el caso de una paciente de sexo femenino quien tiene diagnóstico de AT, con actividad inflamatoria tanto por clínica, laboratorio, RM y PET.

Takayasu arteritis (TA) is a chronic disease that affects principally the aorta. Its etiology persists unknown, nevertheless it is well known that predominates in females and initiates primarily in the youth. This disease seems to has two different stages, an early stage that is characterized by an inflammatory process and a later stage characterized by vascular occlusion. Until now, diagnosis and classification of TA are clinically, based on ACR criteria and imaging studies as computed tomography and aorta angiographies. Actually new imaging, non invasive studies as magnetic resonance (MRI) and positron emission tomography (PET) are allowed. PET technique could be helpfull in the diagnosis and in the detection of inflammatory activity in patients with TA because its capacity to detect increased metabolism. We present the case of a female patient with TA diagnosis, which demonstrated clinical inflammatory activity and was corroborated by laboratory studies, MRI and PET.

Análisis de la utilidad de ecocardiografía de contraste y medicina nuclear en afección cardiovascular de origen autoinmune / Analysis of the usefulness of contrast echocardiography and nuclear medicine in cardiovascular affection due to autoimmune diseases

Actualmente, 1 de cada 3 hombres y 1 de cada 10 mujeres desarrolla un evento cardiovascular ateroesclerótico mayor antes de los 60 años, por lo que la enfermedad arterial coronaria continúa siendo un problema de salud pública. Existe una asociación significativa entre enfermedades autoinmunes tales como lupus eritematoso sistémico, artritis reumatoide y ateroesclerosis coronaria prematura o acelerada. Los objetivos del estudio fueron: a) Valorar la perfusión miocárdica en pacientes con enfermedades reumatológicas, mediante ecocardiografia de contraste (EC) y establecer su utilidad comparando con los resultados obtenidos por medicina nuclear como método de referencia (MN). b) Evaluar la prevalencia de alteraciones en la perfusión miocárdica subclínica en enfermedades autoinmunes y establecer una estrategia para evaluar los cambios cardiovasculares en este padecimiento. Se estudiaron mediante EC en reposo y en el pico máximo del estrés y MN a 37 pacientes pertenecientes a la Consulta externa del Departamento de Reumatología para valorar la perfusión miocárdica del ventrículo izquierdo. La prevalencia de alteraciones en la perfusión miocárdica en síndrome antifosfolípido primario (SAFP), lupus eritematoso y artritis reumatoide por EC y MN, cuando estos métodos se analizaron en forma independiente o juntos fue del 27%. El valor predictivo positivo de ambas pruebas fue del 80%, la sensibilidad del 80% y la especificidad del 93%. En los pacientes con SAFP se encontró que cuando se realizan ambas pruebas diagnósticas la MN alcanza una sensibilidad del 100% si el EC es positivo y una especificidad del 100% cuando el EC negativo. Podemos concluir que es importante determinar la existencia de enfermedad coronaria subclínica en los pacientes con enfermedades inmunológicas mediante estudios no invasivos (Sestamibi SPECT y/o ecocardiografía de contraste) que permiten valorar la perfusión miocárdica.

A significant correlation between autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and premature or accelerated coronary atherosclerosis was found. The objectives of the study were: a) evaluate myocardial perfusion in patients with rheumatic diseases by means of contrast echocardiography (CE) and to establish its usefulness as compared to the results obtained by nuclear medicine (NM) (reference method), b) evaluate the prevalence of alterations in subclinical myocardial perfusion in autoimmune diseases and to establish a strategy to evaluate the cardiovascular changes in this disease. Myocardial perfusion in 37 outpatients of the rheumatology department was evaluated by CE at rest and with pharmacological stress (dobutamine) and NM. The prevalence of alterations in the myocardial perfusion in autoimmune diseases by CE and NM, when these methods were analyzed independently or when both methods were used was 27%. The positive predictive value (PPV) and negative predictive value (NPV) of both tests was 80% and 93%, respectively, the sensitivity was 80% and the specificity was 93%. The prevalence of alterations of perfusion in the primary antiphospholipid syndrome (PAPS) was of 30%. In this patients it was found that when both diagnostic tests are performed, NM reaches a sensitivity of 100% if the CE is positive and an specificity of 100% when the CE is negative. We can conclude that it is important to determine the presence of subclinic coronary artery disease in patients with autoimmune disease by noninvasive studies such as Sestamibi SPECT and/or CE for assessment of myocardial perfusion in order to plan an adequate treatment and follow-up.

Dehidroepiandrosterona en el manejo del lupus eritematoso sistémico / Dehydroepiandrosterone in the management of systemic lupus erythematosus

Los glucocorticoides son base de la terapéutica del Lupus Eritematoso Sistémico (LES). En ocasiones el control de la enfermedad requiere dosis altas que resultan inconvenientes. Los pacientes con LES tienen defectos hormonales que resultan en bajos niveles séricos de andrógenos, principalmente dehidroepiandrosterona (DHEA). En estudios recientes la administración de DHEA permitió reducir la dosis de glucocorticoides necesaria para controlar la enfermedad. Objetivo. Corroborar el papel coadyuvante de la DHEA en el tratamiento de LES. Métodos. Diez mujeres con LES de leve a moderada actividad y múltiples manifestaciones clínicas recibieron 200 mg/día de DHEA por vía oral así como otros medicamentos clínicamente indicados. Las pacientes fueron evaluadas mensualmente a través de MEX-SLEDAI, un cuestionario, una escala visual analógica y estudios de laboratorio. Resultados. Ocho pacientes completaron el estudio. Después de 3 meses de tratamiento con DHEA mejoraron los índices de actividad de LES incluyendo la puntuación MEX-SLEDAI y la sensación de bienestar de los pacientes (78.4 por ciento y 24.7 por ciento respectivamente). La DHEA fue bien tolerada; los efectos adversos observados fueron menores y reversibles al suspender el fármaco.Conclusión. La DHEA parece ser un coadyuvante útil en el tratamiento de LES.