RESUMEN
A relevant role of osteopontin (OPN) and gremlin 1 (Grem1) in regulating cardiac tissue remodeling and formation of heart failure (HF) are documented, with the changes of OPN and Grem1 levels in blood plasma due to acute ischemia, ischemic heart disease-induced advanced HF or dilatative cardiomyopathy being the primary focus in most of these studies. However, knowledge on the early OPN and Grem1 proteins expression changes within cardiomyocytes during remodeling due to chronic ischemia remains insufficient. The aim of this study was to determine the OPN and Grem1 proteins expression changes in human cardiomyocytes at different stages of ischemic HF. A semi-quantitative immunohistochemical analysis was performed in 105 myocardial tissue samples obtained from the left cardiac ventricles. Increased OPN immunostaining intensity was already detected in the stage A HF group, compared to the control group (p < 0.001), and continued to increase in the stage B HF (p < 0.001), achieving the peak of immunostaining in the stages C/D HF group (p < 0.001). Similar data of Grem1 immunostaining intensity changes in cardiomyocytes were documented. Significantly positive correlations were detected between OPN, Grem1 expression in cardiomyocytes and their diameter as well as the length, in addition to positive correlation between OPN and Grem1 expression changes within cardiomyocytes. These novel findings suggest that OPN and Grem1 contribute significantly to reorganization of cellular geometry from the earliest stage of cardiomyocyte remodeling, providing new insights into the ischemic HF pathogenesis.
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Insuficiencia Cardíaca , Péptidos y Proteínas de Señalización Intercelular , Isquemia Miocárdica , Miocitos Cardíacos , Osteopontina , Osteopontina/metabolismo , Osteopontina/genética , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Humanos , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/patología , Masculino , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/patología , Persona de Mediana Edad , Femenino , AncianoRESUMEN
Background and Objectives: The combination of aortic valve stenosis (AS) and ischemic heart disease (IHD) is quite common and is associated with myocardial fibrosis (MF). The purpose of this study was to evaluate the association between the histologically verified left ventricular (LV) MF and its geometry and function in isolated AS and AS within IHD groups. Materials and Methods: In a single-center, prospective trial, 116 patients underwent aortic valve replacement (AVR) with/without concomitant surgery. The study population was divided into groups of isolated AS with/without IHD. Echocardiography was used, and LV measurements and aortic valve parameters were obtained from all patients. Myocardial tissue was procured from all study patients undergoing elective surgery. Results: There were no statistical differences between isolated AS and AS+IHD groups in LV parameters or systolic and diastolic functions during the study periods. The collagen volume fraction was significantly different between the isolated AS and AS+IHD groups and was 7.3 ± 5.6 and 8.3 ± 6.4, respectively. Correlations between MF and left ventricular end-diastolic diameter (LVEDD) (r = 0.59, p = < 0.001), left ventricular mass (LVM) (r = 0.42, p = 0.011), left ventricular ejection fraction (LVEF) (r = -0.67, p < 0.001) and an efficient orifice area (EOA) (r = 0.371, p = 0.028) were detected in isolated AS during the preoperative period; the same was observed for LVEDD (r = 0.45, p = 0.002), LVM (r = 0.36, p = 0.026), LVEF (r = -0.35, p = 0.026) and aortic annulus (r = 0.43, p = 0.018) in the early postoperative period; and LVEDD (r = 0.35, p ≤ 0.05), LVM (r = 0.43, p = 0.007) and EOA (r = 0.496, p = 0.003) in the follow-up period. In the group of AS and IHD, correlations were found only with LV posterior wall thickness (r = 0.322, p = 0.022) in the follow-up period. Conclusions: Histological MF in AS was correlated with LVM and LVEDD in all study periods. No correlations between MF and LV parameters were found in aortic stenosis in the ischemic heart disease group across all study periods.
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Estenosis de la Válvula Aórtica , Ecocardiografía , Fibrosis , Ventrículos Cardíacos , Humanos , Estenosis de la Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/patología , Ecocardiografía/métodos , Miocardio/patología , Función Ventricular Izquierda/fisiología , Isquemia Miocárdica/fisiopatología , Isquemia Miocárdica/complicacionesRESUMEN
OBJECTIVES: To evaluate the association between histologically verified left ventricular (LV) myocardial fibrosis (MF) and its bio- and functional markers with pulmonary hypertension (PH) in severe aortic stenosis (AS). METHODS: About 34 patients with isolated severe AS underwent 2D echocardiography, cardiac magnetic resonance (CMR) imaging, and plasma NT-proBNP evaluation before aortic valve replacement (AVR). LV measurements were analyzed by CMR and LV strain using feature tracking software (Medis Suite QStrain 2.0). Myocardial biopsy sampled at the time of AVR was assessed by a histomorphometric analysis. PH was defined as pulmonary artery systolic pressure (PASP) ⩾ 45 mm Hg. RESULTS: Patients with severe AS and PH (mean PASP 53 ± 3.7 mm Hg) had higher extent of diffuse MF versus patients without PH (12 (10.4-12.7)% vs 6.6 (4.6-8.2)% (p = 0.00)). The extent of diffuse MF correlated with LV dilatation (r = 0.7, p = 0.02), indices of LV dysfunction (lower ejection fraction (r = -0.6, p < 0.001), global longitudinal (r = -0.5, p = 0.02) and circumferential strain (r = -0.5, p = 0.05), elevated NT-proBNP (r = 0.5, p = 0.005) and elevated PASP (r = 0.6, p < 0.001)). Histological MF > 10% (AUC 94.9%), LV global longitudinal strain > -15.5% (AUC 86.3%), and NT-proBNP > 2090 ng/l (AUC 85.1%) were independent predictors of PH in severe AS. CONCLUSIONS: The extent of diffuse myocardial fibrosis in combination with reduced longitudinal left ventricular strain and increased plasma levels of NT-proBNP relates to pulmonary hypertension in severe aortic stenosis.
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Estenosis de la Válvula Aórtica , Hipertensión Pulmonar , Humanos , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/patología , Ventrículos Cardíacos , Fibrosis , Función Ventricular Izquierda , Volumen SistólicoRESUMEN
Although major pathogenesis mechanisms of heart failure (HF) are well established, the significance of early (mal)adaptive structural changes of cardiomyocytes preceding symptomatic ischemic HF remains ambiguous. The aim of this study is to present the morphological characterization of changes in cardiomyocytes and their reorganization of intermediate filaments during remodeling preceding symptomatic ischemic HF in an adult human heart. A total of 84 myocardial tissue samples from middle-left heart ventricular segments were analyzed histomorphometrically and immunohistochemically, observing the cardiomyocyte's size, shape, and desmin expression changes in the remodeling process: Stage A of HF, Stage B of HF, and Stages C/D of HF groups (ACC/AHA classification). Values p < 0.05 were considered significant. The cellular length, diameter, and volume of Stage A of HF increased predominantly by the diameter vs. the control group (p < 0.001) and continued to increase in Stage B of HF in a similar pattern (p < 0.001), increasing even more in the C/D Stages of HF predominantly by length (p < 0.001). Desmin expression was increased in Stage A of HF vs. the control group (p < 0.001), whereas it was similar in Stages A and B of HF (p > 0.05), and most intense in Stages C/D of HF (p < 0.001). Significant morphological changes of cardiomyocytes and their cytoskeletal reorganization were observed during the earliest remodeling events preceding symptomatic ischemic HF.
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Insuficiencia Cardíaca , Miocitos Cardíacos , Adulto , Humanos , Miocitos Cardíacos/metabolismo , Desmina/metabolismo , Insuficiencia Cardíaca/metabolismo , Miocardio/metabolismo , Isquemia/metabolismo , Remodelación VentricularRESUMEN
The angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1-7)-Mas receptor axis plays a significant role in regulating myocardial remodeling and the development of heart failure (HF), with ACE2 being the primary focus. However, contemporary understanding of the membrane-bound form of the human ACE2 protein remains insufficient. The purpose of this study was to determine the expression of ACE2 protein in different cells of the left ventricular myocardium in non-diseased hearts and at various stages of ischemic HF. A total of 103 myocardial tissue samples from the left ventricle underwent quantitative and semi-quantitative immunohistochemical analysis. Upon assessing ACE2 immunostaining in all myocardial cells through unselective digital image analysis, there was no change in the stage A HF group. Nevertheless, the expression of ACE2 membrane protein in cardiomyocytes showed a tendency to increase, while non-cardiomyocyte ACE2 expression decreased significantly (p < 0.001). In the stage B HF group, the intensity of ACE2 immunostaining continued to increase with rising cardiomyocyte ACE2 expression (p < 0.001). Non-cardiomyocyte expression, in contrast, remained similar to that observed in the stage A HF group. In the stages C/D HF group, ACE2 expression reached its highest level in cardiomyocytes (p < 0.001), while ACE2 expression in non-cardiomyocytes was the lowest (p < 0.001). These changes in ACE2 protein levels are associated with left ventricular remodeling in ischemic HF.
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Enzima Convertidora de Angiotensina 2 , Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/metabolismo , Miocardio/metabolismo , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/metabolismoRESUMEN
Magnesium-sensitive transient receptor potential melastatin (TRPM) ion channels, TRPM6 and TRPM7, are present in several organs, but their roles in the heart remain unclear. Therefore, here, we studied the expression patterns of TRPM6 and TRPM7 in normal and diseased myocardium. Cardiac atrial tissue and cardiomyocytes were obtained from healthy pigs and undiseased human hearts as well as from hearts of patients with ischemic heart disease (IHD) or atrial fibrillation (AF). Immunofluorescence and ELISA were used to detect TRP proteins. TRPM6 and TRPM7 immunofluorescence signals, localized at/near the cell surface or intracellularly, were detected in pig and human atrial tissues. The TRP channel modulators carvacrol (CAR, 100 µM) or 2-aminoethoxydiphenyl borate (2-APB, 500 µM) decreased the TRPM7 signal, but enhanced that of TRPM6. At a higher concentration (2 mM), 2-APB enhanced the signals of both proteins. TRPM6 and TRPM7 immunofluorescence signals and protein concentrations were increased in atrial cells and tissues from IHD or AF patients. TRPM6 and TRPM7 proteins were both detected in cardiac atrial tissue, with relatively similar subcellular localization, but distinctive drug sensitivity profiles. Their upregulated expression in IHD and AF suggests a possible role of the channels in cardiac atrial disease.
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Fibrilación Atrial , Canales Catiónicos TRPM , Humanos , Porcinos , Animales , Fibrilación Atrial/metabolismo , Canales Catiónicos TRPM/genética , Canales Catiónicos TRPM/metabolismo , Atrios Cardíacos/metabolismo , Miocitos Cardíacos/metabolismo , Magnesio/metabolismo , Membrana Celular/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismoRESUMEN
Exposure to cadmium (Cd) is known to alter immune responses. Acanthopanax senticosus (Rupr. et Maxim.) Harms (AS) extract, an antioxidant-containing complex of phenolic compounds, tetracyclic triterpenoids/steroids, and polysaccharides, is known to produce Cd mobilization and excretion in vivo. Building upon earlier findings, the aim of the study was to evaluate the effects of an AS extract on Cd accumulation and changes in the presence of splenic immune cells in hosts during a chronic metal exposure. Chronic Cd exposure of BALB/c mice was induced by providing them solutions containing different levels of CdCl2 (25 or 250 mg/L) in double-distilled water, with/without a concurrent presence of AS root extract (approximately 151 g material/L), for 8 wk. At the study end, Cd levels in spleen were measured. Levels of key splenic immune cells, including macrophages, T-lymphocytes, and B-lymphocytes, were determined by immunohistochemistry using, respectively, CD68, CD3, and CD20 antibodies. The results indicated that chronic consumption of AS extract in the presence of the high dose of CdCl2 led to a significant decrease in Cd levels in mouse spleen. The effects of AS on the lower CdCl2 dose were less apparent. In addition, the presence of AS and Cd increased the amount of macrophages and both B and T lymphocytes in mouse spleen relative to concentrations that were lowered as a result of chronic metal only intake.
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Cloruro de Cadmio/farmacocinética , Cloruro de Cadmio/toxicidad , Eleutherococcus/química , Extractos Vegetales/farmacología , Bazo/efectos de los fármacos , Bazo/inmunología , Animales , Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Relación Dosis-Respuesta a Droga , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos BALB C , Raíces de Plantas/química , Bazo/citología , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismoRESUMEN
This study investigates the therapeutic potential of human placental mesenchymal stem cells (P-MSCs) and their extracellular vesicles (EVs) in a murine model of acute respiratory distress syndrome (ARDS), a condition with growing relevance due to its association with severe COVID-19. We induced ARDS-like lung injury in mice using intranasal LPS instillation and evaluated histological changes, neutrophil accumulation via immunohistochemistry, bronchoalveolar lavage fluid cell count, total protein, and cytokine concentration, as well as lung gene expression changes at three time points: 24, 72, and 168 h. We found that both P-MSCs and EV treatments reduced the histological evidence of lung injury, decreased neutrophil infiltration, and improved alveolar barrier integrity. Analyses of cytokines and gene expression revealed that both treatments accelerated inflammation resolution in lung tissue. Biodistribution studies indicated negligible cell engraftment, suggesting that intraperitoneal P-MSC therapy functions mostly through soluble factors. Overall, both P-MSC and EV therapy ameliorated LPS-induced lung injury. Notably, at the tested dose, EV therapy was more effective than P-MSCs in reducing most aspects of lung injury.
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Vesículas Extracelulares , Lesión Pulmonar , Células Madre Mesenquimatosas , Síndrome de Dificultad Respiratoria , Embarazo , Humanos , Animales , Femenino , Ratones , Lesión Pulmonar/terapia , Modelos Animales de Enfermedad , Lipopolisacáridos/metabolismo , Distribución Tisular , Placenta/metabolismo , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/metabolismo , Vesículas Extracelulares/metabolismo , Citocinas/metabolismo , Células Madre Mesenquimatosas/metabolismoRESUMEN
Elsholtzia ciliata essential oil (E. ciliata) has been reported to have an impact on the cardiovascular system. However, its toxicity remains unknown. Therefore, the objective of this investigation was to evaluate the toxicological aspects of the E. ciliata extract. Male Balb/c mice were subjected to either acute (a single dose administered for 24 h) or sub-chronic (daily dose for 60 days) intraperitoneal injections of the E. ciliata extract. The mice were assessed for blood hematological/biochemical profiles, mitochondrial functions, and histopathological changes. Additionally, in vitro cytotoxicity assessments of the E. ciliata extract were performed on immobilized primate kidney cells (MARC-145, Vero) and rat liver cells (WBF344) to evaluate cell viability. The control groups received an equivalent volume of olive oil or saline. Our results demonstrated no significant detrimental effects on hematological and biochemical parameters, mitochondrial functions, cellular cytotoxicity, or pathological alterations in vital organs following the intraperitoneal administration of the E. ciliata extract over the 60-day sub-chronic toxicity study. In general, E. ciliata displayed no indications of toxicity, suggesting that the E. ciliata extract is a safe natural product with a well-defined therapeutic and protective index (found to be 90 and 54, respectively) in Balb/c mice.
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Common prognostic factors do not fully predict clinical outcomes in colorectal cancer, one of the most common malignancies in developed countries. Therefore, biological prognostic markers are under investigation. We investigated the prognostic value of expression of matrix metalloproteinases (MMP-2 and MMP-9) and their inhibitors (TIMP-2 and TIMP-3) in rectal carcinoma to predict survival of the patients. Retrospective analysis of clinicopathological findings of 64 patients who underwent rectal resection due to carcinoma and were followed-up from 2 to 96 months (median 48) was performed. Semi-quantitative scoring was used to assess the expression levels of MMP-2, MMP-9, TIMP-2 and TIMP-3 in rectal carcinoma. During the follow-up, 28 patients died. The deceased patients demonstrated significantly higher expression of MMP-9 and lower expression of TIMP-3 in parenchyma of carcinoma and lower expression of TIMP-2 in stroma of carcinoma, compared to survivors. Moreover, the deceased patients were associated with advanced tumor, metastases in lymph nodes and distant metastases. According to univariate analysis longer survival was predicted by lower expression of MMP-9 in parenchymal cells (p = 0.03), tumor size (early tumor) (p = 0.026), absence of metastases in lymph nodes (p = 0.02) or distant metastases (p = 0.04). Multivariate analysis revealed that metastases in lymph nodes, higher expression of MMP-9 in parenchyma, and lower expression of MMP-9 in stromal cells significantly increased mortality. Expression of MMP-9 in rectal carcinoma is a prognostic marker for overall survival. It is important to identify the origin of MMP-9 to predict better overall survival of the patients.
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Biomarcadores de Tumor/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Neoplasias del Recto/enzimología , Neoplasias del Recto/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Neoplasias del Recto/patología , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Inhibidor Tisular de Metaloproteinasa-3/metabolismoRESUMEN
The task of the present study was to investigate the expression of MMP-2 and MMP-9 in recurrent respiratory papillomas (RRP) and accomplish a comparative analysis with those in laryngeal squamous cell carcinoma (LSCC). The immunohistochemical expression of MMP-2 and MMP-9 was investigated in specimens taken from RRP (n = 38) and LSCC (n = 39) patient groups, and the normal tissue of vocal fold (n = 12, control group). The expression of MMP-2 and MMP-9, both in epithelium and stroma cells, was graded on a semiquantitative scale, ranging from 0 (no expression) to 18 points (high expression). Statistically significant differences in the expression of MMP-2 and MMP-9, both in epithelium and stroma among the RRP, LSCC patients and control group (epithelium) with the LSCC group having the highest MMPs expression scores were revealed. However, no statistically significant correlations among expression of MMPs and clinical and/or morphological features were found in the group of RRP patients. The MMP-2 stroma value of 10.4 points was determined as the optimum point (limiting value) for separating RRP and LSCC patient groups. Results of the present study indicate that the expression of both MMP-2 and MMP-9 are up-regulated early in development of laryngeal papillomas, when the benign neoplastic lesion begins and the next determinant step is concerned with the occurrence of malignization. These results seem promising, as they may improve our understanding of the molecular events leading to the papilloma formation and development, however, further research is needed.
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Neoplasias Laríngeas/enzimología , Metaloproteinasa 2 de la Matriz/biosíntesis , Metaloproteinasa 9 de la Matriz/biosíntesis , Recurrencia Local de Neoplasia/enzimología , Papiloma/enzimología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/biosíntesis , Niño , Preescolar , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Neoplasias Laríngeas/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Papiloma/patología , Estudios Retrospectivos , Adulto JovenRESUMEN
Echinacea purpurea L. (Moench) is used in traditional and conventional medicine. However, there is lack of data on the biological activities of primary plant metabolite lectins. The aim of our experiment was to find out how lectin LysM (lysine motif), which was previously purified, affects the immune response in vivo. Eight-week-old BALB/c male mice (n = 15) received four weekly 250 µg/kg peritonial injections of purified Echinacea purpurea L. (Moench) roots' LysM lectin. The control animal group (n = 15) received 50 µL peritoneal injections of fresh Echinacea purpurea L. (Moench) root tincture, and the negative control animal group (n = 15) received 50 µL peritoneal injections of physiological solution. At the fifth experimental week, the animals were sedated with carbon dioxide, and later euthanized by cervical dislocation, and then their blood and spleen samples were collected. The leukocytes' formula and lymphocytes' count was estimated in blood samples, the T lymphocytes' density was evaluated in spleen zones. A statistically significant (p < 0.05) difference between each group was observed in the leukocytes' formula (monocytes' percentage, also little, medium and giant size lymphocytes). The purple coneflower fresh roots' tincture significantly decreased (p < 0.05) the T lymphocytes' quantity in peritoneal lymphoid sheaths (PALS) compared with the physiological solution injection's group (p < 0.05) and the lectin injection's group (p < 0.001). Meanwhile, lectin injections caused a significant (p < 0.01) increase in the T lymphocytes in a spleen PALS zone, compared with the physiological solution and tincture injection's group. Our data suggests that LysM lectin acts as an immunostimulant, while fresh purple coneflower tincture causes immunosuppression.
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The expression of the channels-enzymes TRPM6 and TRPM7 in the human heart remains poorly defined, and TRPM6 is generally considered not to be expressed in cardiomyocytes. We examined their expression at protein and mRNA levels using right atrial samples resected from patients (n = 72) with or without ischemic heart disease (IHD) and samples from all chamber walls of explanted human hearts (n = 9). TRPM6 and TRPM7 proteins were detected using immunofluorescence on isolated cardiomyocytes, ELISA on tissue homogenates, and immunostaining of cardiac tissue, whereas their mRNAs were detected by RT-qPCR. Both TRPM6 and TRPM7 were present in all chamber walls, with TRPM7 being more abundant. TRPM6 was co-expressed with TRPM7. The expression levels were dependent on cell incubation conditions (presence or absence of divalent cations, pH of the extracellular milieu, presence of TRP channel inhibitors 2-aminoethoxydiphenyl-borate and carvacrol). These drugs reduced TRPM7 immunofluorescence but increased that of TRPM6. TRPM6 and TRPM7 expression was increased in tissues from IHD patients. This is the first demonstration of the presence and co-expression of TRPM6 and TRPM7 in cardiomyocytes from all chamber walls of the human heart. The increased TRPM6 and TRPM7 expression in IHD suggests that the chanzymes are involved in the pathophysiology of the disease.
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Expresión Génica , Isquemia Miocárdica/metabolismo , Miocitos Cardíacos/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Canales Catiónicos TRPM/genética , Canales Catiónicos TRPM/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Cationes Bivalentes/metabolismo , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Técnica del Anticuerpo Fluorescente/métodos , Humanos , Magnesio/metabolismo , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/genética , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodosRESUMEN
Echinacea purpurea (L.) Moench (EP) is a well-studied plant used for health benefits. Even though there are a lot of data on EP secondary metabolites, its active proteins are not studied well enough. The aim of our experiment was to purify lectin fraction from EP roots and evaluate its biological activity in vitro as well as its effect on kidney morphology in vivo. An EP root glycoprotein fraction was purified by affinity chromatography, identified by LC-MS/MS, and used for biological activity tests in vitro and in vivo. Identified glycoproteins were homologous with the LysM domain containing lectins from the Asteraceae plants Helianthus annuus L., Lactuca sativa L., Cynara cardunculus L. A purified fraction was tested by hemagglutination and hemagglutination inhibition (by carbohydrate reactions) in vitro. We purified the hemagglutinating active ~40 kDa size lactose, D-mannose, and D-galactose specific glycoproteins with two peptidoglycan binding LysM (lysine motif) domains. Purified LysM lectin was tested in vivo. Eight-week old Balb/C male mice (n = 15) were treated with 5 µg of the purified lectin. Injections were repeated four times per week. At the fifth experimental week, animals were sedated with carbon dioxide, then euthanized by cervical dislocation and their kidney samples were collected. Morphological changes were evaluated in hematoxylin and eosin stained kidney samples. The purified LysM lectin induced a statistically significant (p < 0.05) kidney glomerular vacuolization and kidney tubular necrosis (p < 0.001).
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Echinacea , Riñón/efectos de los fármacos , Lectinas de Plantas/toxicidad , Animales , Echinacea/genética , Eritrocitos/efectos de los fármacos , Hemaglutinación/efectos de los fármacos , Riñón/patología , Masculino , Ratones , Raíces de Plantas , Conejos , TranscriptomaRESUMEN
BACKGROUND: The majority of deaths due to acute coronary heart disease (CHD) occur outside hospital, unexpectedly, within the first few hours following the onset of the terminal event. Data on the incidence and nature of acute pathological findings in the affected hearts as seen in routine autopsies are somewhat controversial. Detailed pathological examination of coronary arteries and myocardium of such decedents was performed to clarify the situation. METHODS AND RESULTS: Full autopsy and detailed macroscopic and microscopic examination of the coronary arteries and myocardium were performed in 170 men, all registered in the Kaunas Acute Myocardial Infarct Register, who died outside hospital of CHD within 6 hours from the onset of symptoms. Out-of-hospital coronary death was in all cases related to acute ischaemic myocardial lesions, either myocardial infarction (MI) in 92.9% of cases or patchy micronecrosis in 7.1%. In the former group, the following stages of acute infarction were found: early MI (hyperacute phase) in 48.8% of cases, definite MI (displaying grossly identifiable coagulative necrosis) in 21.8% and progressing MI (presence of signs of early MI adjacent to a healing infarction) in 22.3%. Signs of new thrombotic coronary events were found in relation to these acute ischaemic myocardial lesions in 88.8% of cases, as occlusive thrombus in 41.2%, non-occlusive, mural thrombus in 37.0% and microthrombi/microemboli in intramyocardial vessels in 10.6%. CONCLUSIONS: Out-of-hospital coronary death most commonly was related to the early or definite stages of myocardial infarction. Accurate identification of these acute ischaemic lesions was based on detailed microscopic examination of the entire ventricular myocardium, with consideration being paid to signs of cardiomyocyte involvement and early inflammatory reaction associated with it. Acute pathology of the affected coronary artery usually confirmed that these myocardial infarct lesions were the cause of the sudden out of-hospital CHD-related deaths.
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Enfermedad de la Arteria Coronaria/mortalidad , Vasos Coronarios/patología , Servicios Médicos de Urgencia , Infarto del Miocardio/mortalidad , Enfermedad Aguda , Adulto , Anciano , Autopsia , Enfermedad de la Arteria Coronaria/patología , Enfermedad de la Arteria Coronaria/fisiopatología , Progresión de la Enfermedad , Femenino , Ventrículos Cardíacos/patología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Factores de RiesgoRESUMEN
OBJECTIVE: Vocal fold polyps are the most common benign laryngeal lesions. Matrix metalloproteinases (MMP) play an important role in the physiological and pathological remodeling of tissues. The most important subgroup of MMP family consists of gelatinases A and B (MMP-2 and MMP-9). The objective of this study was investigation of the expression of MMP-2 and MMP-9 in vocal fold polyps and normal tissue of vocal folds. MATERIAL AND METHODS: The immunohistochemical expression of MMP-2 and MMP-9 was investigated in specimens taken by endolaryngeal microsurgery from vocal fold polyps (n=30) and normal tissue of vocal fold (n=13, control group). Expression of MMP-2 and MMP-9, both in epithelium and stroma cells, was graded on a semiquantitative scale, ranging from 0 (no expression) to 6 points (high expression). RESULTS: A statistically significant increase was observed in the expression of MMP-2 in stroma cells (P=0.0176) of vocal fold polyps compared to control vocal fold group, whereas no significant difference in the expression of MMP-2 was found in epithelium cells (P=0.1487). Comparison of expression of MMP-2 and MMP-9 in epithelium cells revealed a statistically significant increase in MMP-9 expression (P<0.01) in both groups. However, there was no statistically significant difference in the expression of MMP-9 between groups of vocal fold polyps and control vocal folds. CONCLUSION: Expression of MMP-2 in stroma was significantly higher in polyps than in normal tissue of vocal folds. Our data draw attention to the role of MMP-2 in the development of vocal fold polyps and necessity of further investigations to define its function in morphogenesis of laryngeal benign, premalignant, and malignant lesions.
Asunto(s)
Enfermedades de la Laringe/enzimología , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Pólipos/enzimología , Pliegues Vocales/enzimología , Adulto , Anciano , Epitelio/enzimología , Femenino , Humanos , Inmunohistoquímica , Enfermedades de la Laringe/etiología , Enfermedades de la Laringe/cirugía , Laringoscopía , Masculino , Microcirugia , Persona de Mediana Edad , Pólipos/etiología , Pólipos/cirugía , Estadísticas no Paramétricas , Células del Estroma/enzimologíaRESUMEN
OBJECTIVE: The aim of the study was to determine ventricular and atrial cardiometric parameters at preinfarction and postinfarction stage of ischemic heart disease. OBJECT AND METHODS: Cardiometric parameters (mass, endocardial surface area, the tracts of flow and outflow, etc.) of 132 men (mean age of 49.7+/-8.9 years) who had died suddenly during prehospital period (within 6 hours) after the first or repeated acute event of "pure" ischemic heart disease were investigated. These patients had no other, except ischemia, factors predisposing myocardial hypertrophy as well as clinical symptoms of heart failure. The decedents were divided into preinfarction (71 men) and postinfarction ischemic heart disease (61 men) groups. RESULTS: At preinfarction stage of ischemic heart disease, mass and endocardial surface area of all parts of the heart were increased, the tracts of flow and outflow--longer. At postinfarction stage, only corresponding left ventricular and atrial parameters were more increased. CONCLUSIONS: Eccentric type of left ventricular hypertrophy (proportional increase of mass and endocardial surface area) and concentric type of right ventricular and right and left atrial hypertrophy (the part of myocardium mass per unit of endocardial area is greater) were determined at preinfarction stage of ischemic heart disease. At postinfarction stage, at least as far as evidence of heart failure is not overt, only the corresponding left ventricular and atrial hypertrophy progresses.
Asunto(s)
Muerte Súbita Cardíaca/patología , Hipertrofia Ventricular Izquierda/patología , Infarto del Miocardio/patología , Isquemia Miocárdica/patología , Miocardio/patología , Adulto , Autopsia , Cardiomegalia/patología , Cardiomegalia/fisiopatología , Circulación Coronaria , Interpretación Estadística de Datos , Progresión de la Enfermedad , Hemodinámica , Técnicas Histológicas , Humanos , Hipertrofia Ventricular Izquierda/fisiopatología , Modelos Lineales , Masculino , Persona de Mediana Edad , Contracción Miocárdica , Infarto del Miocardio/mortalidad , Infarto del Miocardio/fisiopatología , Isquemia Miocárdica/mortalidad , Isquemia Miocárdica/fisiopatología , Remodelación VentricularRESUMEN
OBJECTIVE: The aim of the study was to detect changes in left ventricular cardiomyocyte size and shape in response to chronic ischemia and loss of cardiac tissue (myocardial infarction) during the course of ischemic heart disease (IHD). MATERIAL AND METHODS: Left ventricular cardiomyocyte dimensions (diameter and length) were estimated histomorphometrically, and their cross-sectional area and volume were assessed in 85 males who died suddenly out of hospital (within 6 hours of the onset of the terminal event) due to the acute first (preinfarction IHD group, n=53, aged 48.6+/-2.9 years) or repeated (postinfarction IHD group, n=32, aged 51.7+/-2.9 years) IHD attack, and had no other causes for the increased heart load. Twenty-nine males of similar age (mean age, 46.0+/-3.1 years) who succumbed to external causes served as controls. RESULTS: We have found cardiomyocyte hypertrophy in the preinfarction IHD group already. The cardiomyocyte volume was increased by 32.0% in comparison with the same index in the control group, and cross-sectional area and length--by 17.2 and 12.5%, respectively. In postinfarction IHD group, all studied cardiomyocyte parameters did not differ significantly from the analogous indices in the preinfarction IHD group (P>0.05). Cardiomyocyte hypertrophy was related to the increase in left ventricular cardiomyocyte parameters. CONCLUSIONS: Left ventricular cardiomyocyte hypertrophy occurs before the first myocardial infarction. In postinfarction myocardium, cardiomyocyte dimensions do not differ significantly at least prior to the appearance of congestive heart failure syndrome.
Asunto(s)
Infarto del Miocardio/patología , Isquemia Miocárdica/patología , Miocitos Cardíacos/patología , Análisis de Varianza , Autopsia , Ventrículos Cardíacos/patología , Humanos , Hipertrofia Ventricular Izquierda/patología , Masculino , Persona de Mediana Edad , Miocardio/patología , Remodelación VentricularRESUMEN
Matrix metalloproteinase-3 (MMP-3) degrades extracellular matrix and may lead to development of dilatative pathology of ascending thoracic aorta. Expression of MMP-3 depends upon the 5A/6A polymorphism in the promoter region. An increased number of 5A alleles leads to high expression of MMP-3. Thus, objective of the study was to determine whether the 5A/6A polymorphism in the promoter region of MMP-3 gene is associated with the development of dilatative pathology of ascending thoracic aorta. We studied 76 patients (age ranged from 31 to 81 years; median age, 64 years) who underwent aortic reconstruction surgery due to dilatative pathology of ascending thoracic aorta and a random sample of the population (n=604) aged 25-64 years, all from Lithuania. DNA was analyzed by using real-time polymerase chain reaction to genotype polymorphism 5A/6A at a position -1171 of the MMP3 gene promoter. The prevalence of MMP-3 genotypes was similar in the group of dilatative pathology of ascending thoracic aorta and random sample of population. The frequency of 5A allele did not differ significantly between both groups and was 0.506 and 0.514, respectively. Male carriers of 5A/5A genotype were significantly younger compared with those with the 6A/6A genotype. In conclusion, the frequency of MMP-3 promoter 5A/6A genotypes did not differ between the group of patients with dilatative pathology of ascending thoracic aorta and the random sample of population, but the males with dilatative pathology of ascending thoracic aorta and 5A/5A genotype required aortic reconstruction surgery at the younger age than the males carrying 6A/6A genotype in the MMP-3 promoter region.
Asunto(s)
Aorta Torácica/patología , Aneurisma de la Aorta Torácica/genética , Disección Aórtica/genética , Metaloproteinasa 3 de la Matriz/genética , Polimorfismo Genético , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Alelos , Disección Aórtica/patología , Disección Aórtica/cirugía , Aneurisma de la Aorta Torácica/patología , Aneurisma de la Aorta Torácica/cirugía , ADN/aislamiento & purificación , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores Sexuales , Estadísticas no ParamétricasRESUMEN
OBJECTIVE: The aim of this study was to determine atrial structural remodeling during the development of ischemic heart disease. MATERIAL AND METHODS: Quantitative histomorphometric parameters of interstitial collagen network (the percentage volume, perimeter, number of fibers per field and collagen-cardiomyocyte volume ratio) of the atria of 132 autopsied men (mean age 49.7+/-8.9 years) who had died suddenly (within 6 hours since the onset of terminal heart attack symptoms) due to the first (no postinfarction scars) and repeated (postinfarction scars present) acute "pure" ischemic heart disease were investigated. RESULTS: The main remodeling feature of the wall of the both atria among ischemic heart disease subjects is hypertrophy of cardiomyocytes and hyperplasia of interstitial fibrillar collagen network with the maintenance of the same proportion of contractile myocardium and fibrillar collagen network volume. This proportion in the case of the left atrium persists in both pre- and postinfarction ischemic heart disease groups, while myocardium of the right atrium in preinfarction group subjects is characterized by an excess increase of collagen network as compared to cardiomyocyte hypertrophy, which levels again with that of the control in postinfarction group. CONCLUSIONS: At preinfarction stage of ischemic heart disease, remodeling of both atria develops and progresses in the left atrium at postinfarction stage in the relationship with increase of left ventricular dysfunction.