Function of s100 protein in coronary atherosclerosis / Función de la proteína s100 en aterosclerosis coronaria

SUMMARY: Atherosclerosis is a complex disease whose pathogenesis includes endothelial activation, accumulation of lipids in the subendothelium, formation of foam cells, fat bands and formation of atherosclerotic plaque. These complex mechanisms involve different cell populations in the intimate sub-endothelium, and the S-100 protein family plays a role in a number of extracellular and intracellular processes during the development of atherosclerotic lesions. The aim of this study was to determine the phenotypic characteristics of smooth muscle cells and the consequent expression of S100 protein in atherosclerotic altered coronary arteries in advanced stages of atherosclerosis. 19 samples of right atherosclerotic coronary arteries in stages of fibro atheroma (type V lesion) and complicated lesions (type VI lesion) have been analyzed. According to the standard protocol, the following primary antibodies have been used in the immunohistochemical analysis: a-smooth muscle actin (α-SMA), vimentin and S-100 protein. All analyzed samples have been in advanced stages of atherosclerosis, fibro atheroma (stage V lesions) and complicated lesions (type VI lesions). Most of them have had the structure of a complicated lesion with atheroma or fibro atheroma as a basis, subsequently complicated by disruption (subtype VI a), hemorrhage (subtype VI b) or thrombosis (subtype VI c), as well as by the presence of several complications on the same sample. Marked hypocellularity is present in the subendothelium of plaques. Cell population at plaque margins is characterized by immunoreactivity to α-SMA, vimentin, and S100 protein. Some of these cells accumulate lipids and look like foam cells. In the cell population at the margins of the plaques, smooth muscle cells of the synthetic phenotype are present, some of which accumulate lipids and demonstrate S100 immunoreactivity. Summarizing numerous literature data and our results, we could assume that smooth muscle cells, due to their synthetic and proliferative activity in the earlier stages of pathogenesis, as well as the consequent expression of S100 protein, could accumulate lipids in the earlier stages of atherosclerosis which, in advanced stages analyzed in this study, result in immunoreactivity of foam cells of smooth muscle origin to S100 protein.

RESUMEN: La aterosclerosis es una enfermedad compleja cuya patogenia incluye activación endotelial, acumulación de lípidos en el subendotelio, formación de células espumosas, bandas grasas y formación de placa aterosclerótica. Estos complejos mecanismos involucran diferentes poblaciones celulares en el subendotelio íntimo, y la familia de proteínas S-100 juega un papel en varios procesos extracelulares e intracelulares durante el desarrollo de lesiones ateroscleróticas. El objetivo de este estudio fue determinar las características fenotípicas de las células de músculo liso y la consecuente expresión de la proteína S100 en arterias coronarias alteradas ateroscleróticas en estadios avanzados de aterosclerosis. Se analizaron 19 muestras de arterias coronarias ateroscleróticas derechas en estadios de fibroateroma (lesión tipo V) y lesiones complicadas (lesión tipo VI). Según el protocolo estándar, en el análisis inmunohistoquímico se utilizaron los siguientes anticuerpos primarios: α-actina de músculo liso (α-SMA), vimentina y proteína S-100. Todas las muestras analizadas han estado en estadios avanzados de aterosclerosis, fibroateroma (lesiones estadio V) y lesiones complicadas (lesiones tipo VI). La mayoría de ellos han tenido la estructura de una lesión complicada con ateroma o fibroateroma como base, complicada posteriormente por disrupción (subtipo VI a), hemorragia (subtipo VI b) o trombosis (subtipo VI c), así como por la presencia de varias complicaciones en la misma muestra. La hipocelularidad marcada estaba presente en el subendotelio de las placas. La población celular en los márgenes de la placa se caracterizaba por inmunorreactividad a α-SMA, vimentina y proteína S100. Algunas de estas células acumulan lípidos y parecen células espumosas. En la población celular en los márgenes de las placas, estaban presentes las células de músculo liso de fenotipo sintético, algunas de las cuales acumulaban lípidos y mostraban inmunorreactividad S100. Resumiendo numerosos datos de la literatura y nuestros resultados, podríamos suponer que las células del músculo liso, debido a su actividad sintética y proliferativa en las primeras etapas de la patogénesis, así como la consecuente expresión de la proteína S100, podrían acumular lípidos en las primeras etapas de la aterosclerosis que, en estadios avanzados analizados en este estudio, dan como resultado inmunorreactividad de células espumosas de origen muscular liso a la proteína S100.

Adiponectin and Interleukin-33: Possible Early Markers of Metabolic Syndrome.

Adiponectin is one of the most important molecules in the body's compensatory response to the development of insulin resistance. By trying to maintain insulin sensitivity, increase insulin secretion and prevent inflammation, adiponectin tries to maintain glucose homeostasis. Interleukin-33, which belongs to the group of alarmins, also promotes insulin secretion. Interleukin-33 might be either pro-inflammatory or anti-inflammatory depending on the disease and the model. However, interleukin-33 has shown various protective effects in CVD, obesity and diabetes. The aim of our study was to investigate the association between adiponectin and interleukin-33 in patients with metabolic syndrome. As expected, all patients with metabolic syndrome had worse parameters that represent the hallmark of metabolic syndrome compared to the control group. In the subgroup of patients with low adiponectin, we observed less pronounced characteristics of metabolic syndrome simultaneously with significantly higher values of interleukin-33 compared to the subgroup of patients with high adiponectin. Our findings suggested that adiponectin might be an early marker of metabolic syndrome that emerges before anthropomorphic, biochemical and clinical parameters. We also suggest that both interleukin-33 and adiponectin may be used to predict the inflammatory status in the early stage of metabolic syndrome.

Preconditioning with PDE1 Inhibitors and Moderate-Intensity Training Positively Affect Systemic Redox State of Rats.

Taken into consideration that oxidative stress response after preconditioning with phosphodiesterase inhibitors (PDEIs) and moderate physical activity has still not been clarified, the aim of this study was to assess the effects of PDEIs alone or in combination with physical activity, on systemic redox status. The study was carried out on 96 male Wistar albino rats classified into two groups. The first group included animals exposed only to pharmacological preconditioning (PreC) maneuver (sedentary control (CTRL, 1 ml/day saline, n = 12), nicardipine (6 mg/kg/day of NIC, n = 12), vinpocetine (10 mg/kg/day of VIN, n = 12), and nimodipine (NIM 10 mg/kg/day of, n = 12). The second included animals exposed to preconditioning with moderate-intensity training (MIT) on treadmill for 8 weeks. After 5 weeks from the start of training, the animals were divided into four subgroups depending on the medication to be used for pharmacological PreC: moderate-intensity training (MIT+ 1 ml/day saline, n = 12), nicardipine (MIT+ 6 mg/kg/day of NIC, n = 12), vinpocetine (MIT+ 10 mg/kg/day of VIN, n = 12), and nimodipine (MIT+ 10 mg/kg/day of NIM, n = 12). After three weeks of pharmacological preconditioning, the animals were sacrificed. The following oxidative stress parameters were measured spectrophotometrically: nitrites (NO2 -), superoxide anion radical (O2 -), hydrogen peroxide (H2O2), index of lipid peroxidation (TBARS), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH). Our results showed that PDE1 and MIT preconditioning decreased the release of prooxidants and improved the activity of antioxidant enzymes thus preventing systemic oxidative stress.

Asymptomatic Giant Aneurysm of the Left Anterior Descending Coronary Artery: A Case Report and Review of the Literature.

The most common cause of coronary artery aneurysms is atherosclerosis, which is associated with over 50% of all aneurysms diagnosed in adults. Although patients can be asymptomatic throughout their lives, giant coronary artery aneurysms can manifest themselves as myocardial infarction, aneurysmal rupture, and sudden cardiac death as well. Herein, we describe an asymptomatic patient with numerous risk factors and a positive cardiopulmonary exercise test who was admitted to the cardiology clinic for coronary angiography. A giant coronary artery aneurysm (3.0×2.0 cm in diameter) in the left anterior descending coronary artery and significant stenosis in both left and right coronary arteries were found. After discussing possible treatment options, the hospital's heart team recommended the surgical resection of the aneurysm and double coronary artery bypass graft. Four years after the cardiac surgery, at the time of writing the current manuscript, the patient is still in good condition and with no symptoms.

Closure of an atrial septal defect with a one-way flap patch in a patient with severe pulmonary hypertension.

An isolated atrial septal defect (ASD) can occasionally go unrecognized for decades and accounts for 25-30% of congenital heart disease cases diagnosed in adulthood. Pulmonary hypertension often develops as a result of a long-lasting, left-to-right shunt and may ultimately be associated with a fixed increase of pulmonary vascular resistance, sometimes rendering these patients inoperable. To reduce the risk of developing postoperative morbidity and possible mortality, we employed our technique of a unidirectional valved patch for the closure of ASD.

Development of cardiopulmonary bypass ­ A historical review.

The idea of isolated organ perfusion, a precursor of cardiopulmonary bypass, came by Legalois in 1812. First isolated organ perfusion was described by Loebell in 1849. The first closed system for oxygenation and returning the blood through arteries was created by Frey and Gruber in 1885. Gibbon Jr. is considered the father of extracorporeal circulation. In spring of 1934 he began constructing a machine for extracorporeal circulation in Boston. He published the first description of this system in 1937. Gibbon won the grant of the International Business Machines Corporation for developing the machine in 1947. Together they developed Model I in 1949 and Model II in 1951. After a few unsuccessful attempts in 1952, the first successful surgical intervention on the heart (closure of atrial septal defect) using cardiopulmonary bypass was performed on May 6, 1953. In 1945, Kirklin and his working group reported on a series of eight successfully treated patients in a row who underwent surgery with extracorporeal circulation. First successful valve surgery under the direct vision was performed by Dodrill in 1952, using his "Michigan Heart" machine as a right heart bypass. Using cardiopulmonary bypass, cardiac surgeons can deal with the complex cardiac pathology and save millions of lives.