RESUMO
The risk factors that are the most significant for the development of most cardiovascular diseases are arterial hypertension (AH), type 2 diabetes (DM), and inflammation. However, for the development of aortic aneurysms, DM is not one of them. Our study aimed to evaluate the difference between inflammatory infiltration in three individual layers of the ascending aortic aneurysm within diabetic and hypertensive patients. Forty-five patients aged 36 to 80 were divided into a group with diabetic patients without AH (group DM, N=8) and hypertensive patients without DM (group AH, N=37). For the histological analysis, aortic aneurysms were stained with hematoxylin eosin and Movat. We used immunochemical methods to detect pro- (M1), anti-inflammatory (M2) macrophages, T-helper, T-killer cells, B cells, and plasma cells. Statistical analysis was done by independent-samples Kruskal-Wallis test adjusted by Bonferroni correction for multiple tests (P<0.05). We found no difference in the volume density of collagen, elastin, vascular smooth muscle cells (VSMC), and ground substance between groups. In the DM group, there were significantly fewer M2, T-helpers, and T-killers in the media than in the intima and the adventitia (P<0.05). There were no significant differences in the number of M1, B, and plasma cells between all three vascular layers (P<0.05). In the AH group, there were significantly fewer B and plasma cells, T-helper, T-killer cells, M1, and M2 in the media than in the intima and adventitia (P<0.05). Our results conclude that the tunica media in the aneurismal wall of the AH group retained immune privilege. In contrast, in the DM group, all three layers were immune-privileged.
Assuntos
Aneurisma da Aorta Ascendente , Aneurisma Aórtico , Diabetes Mellitus Tipo 2 , Hipertensão , Humanos , Túnica Adventícia , Diabetes Mellitus Tipo 2/complicações , Aneurisma Aórtico/patologia , Hipertensão/complicações , Túnica Íntima/químicaRESUMO
Aortic aneurysms occur relatively frequently in the ascending thoracic aorta, but are rarely seen in patients with type 2 diabetes. Our aim was to evaluate inflammatory cell infiltration in the ascending aortic aneurysm wall in patients with diabetes without arterial hypertension (DM2 group, N=6) versus hypertensive non-diabetic patients (AH group, N=34). For histologic analysis, the sections were stained with hematoxylin-eosin and Movat pentachrome. The immunohistochemical staining was used to analyze the infiltration of pro-inflammatory (CD68) and anti-inflammatory macrophages (CD163), T helper (CD4) and T killer cells (CD8), and B (CD79a) and plasma cells (CD138) in all three layers of aneurysms of both groups. The statistical significance of the differences between groups was evaluated by ANOVA and the Welch test. In comparison to the AH group, the DM2 group developed less severe infiltration of pro-inflammatory macrophages (P=0.004) and B cells (P=0.025) in the tunica intima, and tunica media (P=0.049, P=0.007, respectively), and fewer plasma cells in the tunica media (P=0.024) and tunica adventitia (P=0.017). We found no significant differences in the number of T helper, T killer cells, and anti-inflammatory macrophages and in the amount of collagen and elastic fibers, ground substance, and smooth muscle cells in all three layers of the vessel wall. Except in tunica adventitia of DM2 group, there were more collagen fibers overall (P=0.025). Thus, we conclude that the histological structure of the aneurysm in diabetics without hypertension is almost the same as in hypertensive patients without diabetes. Diabetics had significantly less inflammatory infiltration in all three layers of the vessel wall, and more collagen fibers in tunica adventitia.
Assuntos
Aneurisma Aórtico , Diabetes Mellitus Tipo 2 , Hipertensão , Aneurisma Aórtico/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Humanos , Hipertensão/complicações , Hipertensão/patologia , Túnica Íntima/patologia , Túnica Média/patologiaRESUMO
The patency of the vein graft in coronary artery bypass grafting could be dependent on the conventional open (vsO) or endoscopic (vsE) harvesting and on the hypoxic damage of endothelial cells. We aimed to evaluate both surgical techniques according to endothelial loss that occurs in the time between harvesting and implantation. Twenty-six saphenous veins were divided into vsO (n = 16) and vsE (n = 10) group. Three samples were taken from each vein. The first sample was taken after removal, the second before implantation of the distal part, and the third before the implantation of the proximal part, and they were stained with HE, Movat, and immunohistochemically with CD31. A significant loss of endothelial cells within both groups was found at the time of implantation of the distal and the proximal part of the vein graft compared to the endothelial cells at the time of harvesting. There were no significant differences in the endothelial loss between vsE and vsO groups at the time of harvesting and at the time before the implantation of the distal part. A higher number of endothelial cells was found in vsE group compared to vsO group at the time just before the implantation of the proximal part. The comparison of the implanted portions of vsE and vsO grafts to mammary arteries revealed a significant loss of endothelial cells only in vsO graft. We conclude that, at the time of implantation, the endothelial layer of the vein graft harvested endoscopically is more preserved than of the vein graft harvested openly.
Assuntos
Ponte de Artéria Coronária/métodos , Endotélio Vascular/cirurgia , Veia Safena/cirurgia , Enxerto Vascular , Idoso , Idoso de 80 Anos ou mais , Angiografia Coronária , Endoscopia , Células Endoteliais/citologia , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Hipóxia , Masculino , Artéria Torácica Interna/transplante , Pessoa de Meia-Idade , Projetos PilotoRESUMO
Atherosclerosis is a chronic inflammatory disease of arteries and it affects the structure and function of all three layers of the coronary artery wall. Current theories suggest that the dysfunction of endothelial cells is one of the initial steps in the development of atherosclerosis. The view that the tunica intima normally consists of a single layer of endothelial cells attached to the subendothelial layer and internal elastic membrane has been questioned in recent years. The structure of intima changes with age and it becomes multilayered due to migration of smooth muscle cells from the media to intima. At this stage, the migration and proliferation of smooth muscle cells do not cause pathological changes in the intima. The multilayering of intima is classically considered to be an important stage in the development of atherosclerosis, but in fact atherosclerotic plaques develop only focally due to the interplay of various processes that involve the resident and invading inflammatory cells. The tunica media consists of multiple layers of smooth muscle cells that produce the extracellular matrix, and this layer normally does not contain microvessels. During the development of atherosclerosis, the microvessels from the tunica adventitia or from the lumen may penetrate thickened media to provide nutrition and oxygenation. According to some theories, the endothelial dysfunction of these nutritive vessels may significantly contribute to the atherosclerosis of coronary arteries. The adventitia contains fibroblasts, progenitor cells, immune cells, microvessels, and adrenergic nerves. The degree of inflammatory cell infiltration into the adventitia, which can lead to the formation of tertiary lymphoid organs, correlates with the severity of atherosclerotic plaques. Coronary arteries are surrounded by perivascular adipose tissue that also participates in the atherosclerotic process.
Assuntos
Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/patologia , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/patologia , Túnica Adventícia/patologia , Humanos , Túnica Íntima/patologia , Túnica Média/patologiaRESUMO
Obstructive coronary artery disease (CAD) is characterized by inflammation within the atherosclerotic coronary arteries. Infiltration of inflammatory cells into muscular media can lead to remodeling and weakening of the arterial wall. We examined the relationship between inflammatory infiltration in perivascular adipose tissue (PVAT), state of the external elastic membrane, and the intensity of inflammatory infiltration in the tunica media of coronary arteries obtained by endarterectomy from symptomatic patients with diffuse CAD. We analyzed endarterectomy sequesters from 22 coronary arteries that contained the intima, media, a part of the adventitia, and PVAT in at least one part of the sequester. The coronary arteries were divided into two groups according to the presence or absence of inflammatory infiltration in PVAT. Staining with hematoxylin-eosin and by the Movat's method showed atherosclerotic changes in the intima and media. Immunohistochemistry (anti-leukocyte common antigen [LCA] antibody) was used for the detection of leukocytes. We found a significant positive correlation between inflammatory infiltration in PVAT and preservation of the external elastic membrane of coronary arteries. Furthermore, we found a significant negative correlation between inflammatory infiltration in PVAT and the intensity of inflammatory infiltration in the media. It seems that the integrity of the external elastic membrane and the proinflammatory properties of PVAT restrain inflammatory cells within PVAT. Both effects may prevent the migration of inflammatory cells into the media and delay the development of CAD.
Assuntos
Tecido Adiposo/patologia , Aterosclerose/patologia , Doença da Artéria Coronariana/patologia , Inflamação/patologia , Túnica Média/patologia , Aterosclerose/cirurgia , Doença da Artéria Coronariana/cirurgia , Endarterectomia , Humanos , Leucócitos/patologia , Macrófagos/patologiaRESUMO
In coronary artery disease (CAD), the disruption of the tunica media immune privilege manifests as increased leukocyte infiltration and the formation of vasa vasorum. We aimed to characterize the immune privilege status of the tunica media in human coronary arteries (CAs) with atherosclerotic plaques, by comparing the abundance and composition of immune-cell infiltrates within the individual arterial-wall layers, and by evaluating vasa vasorum neovascularization of the tunica media. The tissue samples were obtained from 36 symptomatic patients with diffuse CAD (aged 60-72 years) who underwent coronary endarterectomy. T and B cells, macrophages and endothelial cells in the CAs were detected by immunohistochemistry. Morphological analysis of CAs showed significant atherosclerotic changes in all specimens. In the media, we observed damage and loss of smooth muscle cells, destruction of the extracellular matrix architecture, and fibrosis. There were 43.3% of immune cells in the intima, 50% in the adventitia, and 6.7% in the media. In the media, 51.1% of the immune cells were T cells (p Ë 0.001 compared to B cells and macrophages; ANOVA, Scheffe post hoc analysis), 23.5% were B cells, and 25.4% were macrophages. The number of vasa vasorum in the media was 1 in 38.9% of CAs, 2-3 in 36.1%, and ≥4 in 25% of CAs. Our results indicate that, in atherosclerotic CAs, the immune privilege of the media is disrupted by the infiltration of T and B cells, macrophages, and the presence of vasa vasorum.
Assuntos
Aterosclerose/patologia , Vasos Coronários/patologia , Túnica Média/patologia , Vasa Vasorum/patologia , Idoso , Aterosclerose/imunologia , Linfócitos B/citologia , Proliferação de Células , Vasos Coronários/imunologia , Células Endoteliais/citologia , Humanos , Imuno-Histoquímica , Leucócitos/citologia , Macrófagos/citologia , Pessoa de Meia-Idade , Placa Aterosclerótica , Linfócitos T/citologia , Túnica Média/imunologia , Vasa Vasorum/imunologiaRESUMO
Diabetic retinopathy (DR) is a complication of diabetes characterized by vascular permeability, increased tissue ischemia, and angiogenesis. One of the most important proteins involved in angiogenesis is vascular endothelial growth factor (VEGF, also known as VEGFA). A previous study demonstrated that two single nucleotide polymorphisms (SNPs), rs6921438 and rs10738760, account for nearly half the variation in circulating VEGF levels. The aim of our study was to assess the association between rs6921438 and rs10738760 and DR in Slovenian patients with type 2 diabetes mellitus (T2DM). This case-control study enrolled 1037 unrelated Slovenian individuals (Caucasians) with T2DM. DR group included 415 T2DM patients with DR, while control group included 622 T2DM patients with no clinical signs of DR. The clinical and laboratory data were obtained from the medical records of the patients. The genotyping of rs6921438 and rs10738760 SNPs was carried out with real-time PCR assays. Significant differences were observed between patients with DR and controls in the duration of diabetes (p < 0.001), insulin therapy (p < 0.001), glycated hemoglobin (p = 0.001), body mass index (p = 0.002), total cholesterol (p = 0.002), and low-density lipoprotein cholesterol (p < 0.001). However, we did not observe significant differences in the genotype and allele distribution of the two SNPs, between DR and control group (p < 0.05). Logistic regression analysis showed that rs6921438 and rs10738760 were not independent genetic risk factors for DR in the co-dominant model adjusted for the above-mentioned clinical and laboratory data. In conclusion, VEGF-related SNPs rs10738760 and rs6921438 are not associated with DR in our group of Slovenian patients (Caucasians) with T2DM.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Retinopatia Diabética/genética , Fator A de Crescimento do Endotélio Vascular/genética , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos de Casos e Controles , Colesterol/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Retinopatia Diabética/epidemiologia , Feminino , Genótipo , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Eslovênia/epidemiologiaRESUMO
In vivo visualization of kidney and liver damage by Magnetic Resonance Imaging (MRI) may offer an advantage when there is a need for a simple, non-invasive and rapid method for screening of the effects of potential nephrotoxic and hepatotoxic substances in chronic experiments. Here, we used MRI for monitoring chronic intoxication with microcystins (MCs) in rat. Male adult Wistar rats were treated every other day for eight months, either with MC-LR (10 µg/kg i.p.) or MC-YR (10 µg/kg i.p.). Control groups were treated with vehicle solutions. T1-weighted MR-images were acquired before and at the end of the eight months experimental period. Kidney injury induced by the MCs presented with the increased intensity of T1-weighted MR-signal of the kidneys and liver as compared to these organs from the control animals treated for eight months, either with the vehicle solution or with saline. The intensification of the T1-weighted MR-signal correlated with the increased volume density of heavily injured tubuli (R2 = 0.77), with heavily damaged glomeruli (R2 = 0.84) and with volume density of connective tissue (R2 = 0.72). The changes in the MR signal intensity probably reflect the presence of an abundant proteinaceous material within the dilated nephrons and proliferation of the connective tissue. T1-weighted MRI-is a valuable method for the in vivo screening of kidney and liver damage in rat models of intoxication with hepatotoxic and nephrotoxic agents, such as microcystins.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Nefropatias/induzido quimicamente , Imageamento por Ressonância Magnética/métodos , Microcistinas/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/patologia , Nefropatias/diagnóstico , Nefropatias/patologia , Masculino , Toxinas Marinhas , Microcistinas/administração & dosagem , Ratos , Ratos WistarRESUMO
Mitochondrial toxin 3-nitropropionic acid (3NPA) is a neurotoxin that inhibits the activity of succinate dehydrogenase, a key enzyme of oxidative energy production, and characteristically provokes neurodegeneration in the striatum, resembling Huntington's disease. 3NPA also affects the activity of glycogen-sinthase-kinase-3b (GSK-3b), an enzyme implicated in glycogen synthesis and in signal transduction. The aim of this study was to evaluate cardiac glycogen content and histopathological changes in the hearts of rats after subchronic treatment with 3NPA.Female adult Wistar rats were treated daily with 30mg/kg of 3NPA subcutaneously 8 days. The control group was treated with normal saline for 8 days. For the comparison of measured parameters between groups we used the Student's t-test (p<0.05). The stereological evaluation of glycogen content in histological sections of the heart was processed with periodic acid-Schiff (PAS). Histochemical procedure showed a significant accumulation of glycogen granules in the 3NPA group (0.028mm(3)/mm(3)±0.022), whereas the hearts of control animals were nearly devoid of glycogen granules (0.002mm(3)/mm(3)±0.001). Haematoxylin-eosin histological staining showed diffuse swelling of cardiomyocytes (3NPA=15.989µm ±1.649; saline=13.456µm ± 0.786), loss of cell cross-striations, lower myofibril volume fraction (3NPA=0.3922mm(3)/mm3 ± 0.0230, saline=0.4550mm(3)/mm3 ± 0.0083), and mononuclear infiltration in the interstitial tissue, mostly along the blood vessels. Sirius red staining showed fibrosis of the heart (3NPA=0.0531mm93)/mm(3)±0.0090, saline=0.0135mm(3)/mm3 ± 0.0051). TUNEL staining showed TUNEL-positive cells in the 3NPA group (2.04cells/mm2 ± 0.92) and almost no TUNEL-positive cells in the saline group (0.27cells/mm2 ± 0.14). This experiment shows that 3NPA-induced histopathological changes in the heart are accompanied by a significant accumulation of glycogen granules in cardiomyocytes.
Assuntos
Glicogênio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Nitrocompostos/toxicidade , Propionatos/toxicidade , Animais , Feminino , Marcação In Situ das Extremidades Cortadas , Miócitos Cardíacos/patologia , Ratos , Ratos WistarRESUMO
Kidney transplantation (Ktx) is generally performed during end stage renal disease due to a loss of the kidneys' ability to filter wastes from the circulatory system. Acute graft-versus-host disease (GVHD) after Ktx is a life-threatening complication that progresses to organ failure, systemic complications, and death. The current study evaluated the significance of histologic findings of GVHD as obtained from skin biopsies following Ktx in swine. A swine model of Ktx with tacrolimus-based immunosuppression was used to assess possible correlations between acute-graft-cellular rejection and skin histological findings for prediction of GVHD. Animals were divided into a Ktx treatment group or a control group with no Ktx and skin and kidney biopsies were histologically assessed at postoperative days 0, 15, 30, 45 and 60. Skin samples were analyzed and classified from grade 1 to 4 of skin GVHD and the major histopathological changes of kidney acute cellular rejection were described using Banff's score system. We observed a significant linear correlation between the histological grading values of skin biopsy changes and the histological grading values of kidney biopsies (Kendall's tau_b=0.993) in the Ktx experimental group. No histological changes were observed in controls. Our findings demonstrate the diagnostic value of staging skin GVHD after Ktx and suggest it's future utility for monitoring long term Ktx-induced changes.
Assuntos
Doença Enxerto-Hospedeiro/patologia , Transplante de Rim/efeitos adversos , Transplante de Rim/patologia , Doença Aguda , Animais , Biópsia , Modelos Animais de Doenças , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Rim/patologia , Pele/patologia , Suínos , Fatores de TempoRESUMO
BACKGROUND: Type 2 diabetes is an important risk factor for the development of coronary artery disease (CAD). Focal or diffuse inflammation is often present in the vessels of patients with CAD. Mast cells are frequently present in the plaques as well as in the inflammatory infiltrates in the atherosclerotic vessel wall. In the study we wanted to examine whether there are differences in the morphology, number and distribution of mast cells and in their ability to modify the atherosclerotic process in coronary arteries (CA) in the diabetic vs. the hypertensive population of patients with CAD. METHODS: Coronary artery endarterectomy specimens were obtained from patients with diabetes or hypertension as the only risk factor for CAD. The specimens were stained with haematoxylin-eosin and Sulphated Alcian Blue for mast cells and with immunofluorescent methods for fibrinogen-fibrin and IgG deposits in the vessel wall. Both morphological and stereological assessments were conducted for mast cells and mononuclear cell infiltrates. RESULTS: The histological analysis of the vessel wall of diabetic patients in comparison with hypertensive patients showed a damaged endothelial cells layer and deposits of fibrin-fibrinogen and IgG in the tunica intima and media. The stereological count revealed a diminished numerical density of mast cells and a significantly higher volume density of the mononuclear cells. Mast cells displayed cytoplasmic vacuolization, extracellular extrusion of granule and pyknotic nuclei. CONCLUSION: This preliminary study suggests that the impaired mast cells might be the reason for more extensive inflammatory and immunologic atherosclerotic changes in the CA vessel wall of CAD patients with type 2 diabetes.
Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/cirurgia , Diabetes Mellitus Tipo 2/complicações , Endarterectomia , Hipertensão/complicações , Mastócitos/imunologia , Idoso , Doença da Artéria Coronariana/imunologia , Doença da Artéria Coronariana/metabolismo , Vasos Coronários/química , Vasos Coronários/imunologia , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/metabolismo , Fibrina/análise , Fibrinogênio/análise , Imunofluorescência , Humanos , Hipertensão/imunologia , Hipertensão/metabolismo , Imunoglobulina G/análise , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Eslovênia , Coloração e Rotulagem/métodosRESUMO
In this study we investigated the association of the interleukin-1 receptor antagonist gene variable number tandem repeat (IL1RN VNTR) polymorphism and of the inhibitor of kappa B-like protein (IKBL) gene polymorphism with myocardial infarction (MI) in a group of patients with type 2 diabetes. The IL1RN VNTR and the IKBL+ 738T > C gene polymorphisms were tested in 374 Caucasians: 151 cases with MI and 223 subjects with no history of coronary artery disease. The IL1RN VNTR polymorphism was not a risk factor for MI in Caucasians with type 2 diabetes (genotype 22 vs. the rest: odds ratio (OR) 1.6; 95% confidence interval (CI) = 0.8-3.5; p = 0.2). We also failed to demonstrate that IKBL+ 738T > C gene polymorphism was associated with MI in patients with type 2 diabetes (OR = 0.9; 95% CI = 0.3-2.6; p = 0.9). We provide evidence that the IL1RN VNTR and the IKBL + 738T > C gene polymorphisms are not risk factors for MI in Caucasians with type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Antígenos de Histocompatibilidade Classe II/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/genética , Proteínas Adaptadoras de Transdução de Sinal , Idoso , Feminino , Predisposição Genética para Doença/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco , Eslovênia/epidemiologiaRESUMO
Intestinal transplantation is being increasingly performed to treat patients with irreversible intestinal failure. The major cause of intestinal graft failure is graft-versus-host disease (GVHD) that represents a life-threatening complication after small bowel transplantation (Itx). The purpose of this study was to assess the diagnostic and prognostic value of skin biopsy histological changes for acute GVHD after Itx in pigs. Thirty-four Large White pigs were divided into three groups: Group 1 with Itx only, Group 2 with Itx and donor bone marrow infusion (Itx BM) and Group 3 (control group - before the operation). Animals received tacrolimus-based immunosuppression from day 0 to day 30 postoperatively. Skin and small bowel biopsies were histologically assessed, analysed and classified from grade 1 to 4 on postoperative days 15, 30, 45 and 60. There was a strong correlation between the histological grading values of skin biopsy changes and the histological grading values of small bowel biopsy changes (Kendall's tau_b is 0.855 for the Itx group and 0.730 for the Itx BM group). The significant correlation found between skin and small bowel histological changes suggests the prognostic value of skin biopsies after Itx. In conclusion, our findings emphasise the diagnostic and prognostic value of skin biopsy analysis for acute GVHD after Itx.
Assuntos
Biópsia/veterinária , Rejeição de Enxerto/diagnóstico , Doença Enxerto-Hospedeiro/diagnóstico , Intestino Delgado/transplante , Pele , Doença Aguda , Animais , SuínosRESUMO
In this study we analyzed the contribution of genetic variability of the insertion/deletion (I/D) polymorphism of the angiotensin-I converting enzyme (ACE) gene to the predisposition for coronary artery disease (CAD) in a group of patients with type 2 diabetes. The I/D ACE gene polymorphism was tested in 366 Caucasians with type 2 diabetes: 148 cases with CAD and 218 subjects with no history of CAD. We failed to demonstrate that the ACE DD genotype was a risk factor for CAD in Caucasians with type 2 diabetes (OR 2.0, 95% CI 0.9-4.7; p = 0.1). In conclusion, we provide evidence that the ACE deletion/deletion genotype is not a risk factor for CAD in Caucasians with type 2 diabetes.
Assuntos
Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Peptidil Dipeptidase A/genética , População Branca/genética , Idoso , Feminino , Deleção de Genes , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
The aim of the study was to prove the long-lasting and continuously harmful effect of chronic Chlamydia pneumoniae (CPn) infection on vessel walls in patients with diffuse coronary artery disease (CAD). In surgically obtained endarterectomized atherosclerotic plaques grade VI-VIII (Stary classification) from 10 patients with diffuse coronary artery disease and chronic (7) or past (3) CPn infection, signs of inflammatory response of the vessel wall on infectious agents were studied. In all 10 endarterectomized plaque step serial sections, immunologic signs of vessel wall response were present (positive T- and B-lymphocytes, macrophages, and capillarogenesis). In 8 of 10 patients' atherosclerotic plaque, unique features of active vasculitis in the neoarteriolar wall as well as arteriologenesis, were found. Seven of these 8 patients had serologically proven chronic CPn infection, and 1 had past infection. Features of vasculitis as well as arteriologenesis were absent in 2 patients who recovered from CPn infection at the time of surgery. In the endarterectomized segments of 3 randomly chosen patients in this study, the polymerase chain reaction method revealed positive DNA of CPn. Two of these patients had chronic infection, but the third had only a past CPn infection. This study provides evidence that CPn infection has continuous and a long-lasting inflammatory response in the high-grade atherosclerotic coronary artery vessel wall.
Assuntos
Infecções por Chlamydophila/complicações , Chlamydophila pneumoniae , Doença das Coronárias/microbiologia , Doença das Coronárias/patologia , Vasos Coronários/microbiologia , Vasos Coronários/patologia , Linfócitos B/imunologia , Chlamydophila pneumoniae/genética , Chlamydophila pneumoniae/isolamento & purificação , Doença Crônica , Ponte de Artéria Coronária , Doença das Coronárias/etiologia , Doença das Coronárias/imunologia , Doença das Coronárias/cirurgia , Vasos Coronários/imunologia , DNA Bacteriano/análise , Progressão da Doença , Endarterectomia , Humanos , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Fatores de Risco , Linfócitos T/imunologia , Fatores de TempoAssuntos
Infecções por Chlamydophila/complicações , Infecções por Chlamydophila/patologia , Chlamydophila pneumoniae , Doença da Artéria Coronariana/microbiologia , Doença da Artéria Coronariana/patologia , Doença Crônica , Doença da Artéria Coronariana/cirurgia , Endarterectomia , Humanos , Masculino , Pessoa de Meia-Idade , Vasculite/microbiologia , Vasculite/patologia , Vasculite/cirurgiaRESUMO
In order to investigate the contribution of the atrial natriuretic factor (ANF) gene in pathogenesis of essential arterial hypertension (EAH), we analyzed the ScaI gene polymorphism of the ANF gene in a group of children with EAH. Fifty-eight children, aged 8-19 years, with the diagnosis of EAH were included in the association study and were compared to 57 subjects with normal blood pressure (the control group). Arterial hypertension was defined as systolic/diastolic blood pressure higher than the 95th age-gender-height percentile of the adopted reference values. We failed to demonstrate an association between the ScaI ANF gene polymorphism and EAH in childhood (OR = 2; 95% CI 0.9-4.2; p = 0.07), however, we provided evidence of an interaction between the ScaI ANF gene polymorphism and obesity defined as BMI over the 85th percentile (OR = 13.1; 95% CI 1.6-106; p < 0.001).
Assuntos
Fator Natriurético Atrial/genética , Predisposição Genética para Doença , Hipertensão/genética , Polimorfismo Genético , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Feminino , Humanos , MasculinoRESUMO
Acute intoxication with MC-LR induces cytoskeletal alterations, apoptosis and necrosis of hepatocytes resulting in intrahepatic hemorrhage. Preliminary results have shown that chronic treatment of rats with intraperitoneal injections of sublethal doses of microcystins MC-LR and MC-YR could induce not only liver, but also kidney injuries. We aimed to investigate whether the induction of the cytoskeletal changes, apoptosis and necrosis could be the mechanisms involved in the injury of kidney cells in the chronic model of microcystin intoxication. Experimental rats were receiving intraperitoneal injections of MC-LR (10 microg/kg) or MC-YR (10 microg/kg) every second day for 8 months, while control rats were receiving only the vehicle. The histopathological investigation revealed collapsed glomeruli with thickened basement membranes and dilated tubuli filled with eosinophilic casts. Rhodamine-phalloidin labeling showed cytoplasmic aggregation and accumulation of fibrilar actin filaments within the epithelial tubular cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) showed increased number of TUNEL-positive cells in the kidney cortex and medulla. The pathological changes induced by MC-LR appeared more severe than those induced by MC-YR. The results support the view that at the cellular level, the mechanisms that underly the chronic nephrotoxicity are similar to the mechanisms of the acute hepatotoxicity of microcystins.
Assuntos
Toxinas Bacterianas/toxicidade , Citoesqueleto/efeitos dos fármacos , Rim/efeitos dos fármacos , Peptídeos Cíclicos/toxicidade , Análise de Variância , Animais , Apoptose/efeitos dos fármacos , Proteínas do Citoesqueleto/efeitos dos fármacos , Citoesqueleto/patologia , Inibidores Enzimáticos/toxicidade , Rim/patologia , Masculino , Toxinas Marinhas , Microcistinas , Necrose , Ratos , Ratos Wistar , Circulação Renal/efeitos dos fármacos , Testes de Toxicidade CrônicaRESUMO
INTRODUCTION: The aim of the study was to evaluate the role of apoptosis, proliferation markers, volume density of interstitium, and myofibril volume fraction for the prognosis in patients with end-stage dilated cardiomyopathy (DCM). METHODS: Endomyocardial biopsy was performed during open-heart surgery in 56 patients with end-stage DCM. Patients were divided into two groups, one group with shorter survival (24+/-9 months, mean+/-S.D.) and another group with survival of more than 7 years after operation. The TUNEL method was used for the detection of apoptosis, and immunohistochemical methods were used for the evaluation of inhibitor of apoptosis (bcl-2) and proliferation markers (PCNA and Ki-67). RESULTS: The increased percentage of apoptotic myocytes, decreased expression of bcl-2, and decreased expression of PCNA and Ki-67 antigen was found in the group with early mortality compared to that with longer survival. Myofibril volume fraction was lower and volume density of interstitium was higher in the group with early mortality compared to that with longer survival. CONCLUSION: Apoptosis, bcl-2 expression, and proliferation activity of myocytes, myofibril volume fraction, and volume density of interstitial tissue might be useful in predicting the prognosis (progressive vs. nonprogressive form) of patients with heart failure due to DCM.
Assuntos
Apoptose , Biomarcadores/análise , Cardiomiopatia Dilatada/patologia , Miócitos Cardíacos/patologia , Adulto , Idoso , Biópsia , Cardiomiopatia Dilatada/mortalidade , Divisão Celular , Feminino , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Antígeno Ki-67/biossíntese , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Valor Preditivo dos Testes , Prognóstico , Antígeno Nuclear de Célula em Proliferação/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/biossínteseRESUMO
The aims of the study were to investigate the histopathologic characteristics of atherosclerotic lesions and to evaluate the role of apoptosis or programmed cell death in diffuse coronary atherosclerosis. The study included 59 patients who underwent coronary artery bypass grafting coupled with coronary endarterectomy because of diffuse coronary atherosclerosis. Histopathologic analysis of endarterectomy sequesters showed atheroma with confluent extracellular lipid core-type IV lesions in 13 cases (22%); atheroma with lipid core and a cap of fibromuscular layers-type V lesions in 9 cases (15.3%); predominantly calcified fibrous tissue-type VII lesions in 13 cases (22%); and predominantly fibrous tissue-type VIII lesions in 24 cases (40.7%). TUNEL-positive cells were observed in 4 endarterectomy sequesters (6.8%) of subjects with diffuse coronary atherosclerosis. TUNEL-positive cells were demonstrated in the area of mononuclear infiltrates as well as in the vessel wall. The percentage of TUNEL-positive cells in mononuclear infiltrates was 0.5%. Intense mononuclear infiltrates in tunica intima were found in 50% of sequesters, and they consisted of macrophages (40%), T-lymphocytes (17%), and B-lymphocytes (14%). In the area of infiltrates the proportion of MIB-1-positive cells was 2.7%, which was higher than in the intima outside the area of infiltrates (0.5%). In conclusion, apoptosis, which is confined to mononuclear infiltrates, is most likely involved in the development of diffuse coronary atherosclerosis; however, the percentage of apoptotic cells was low (0.5%). A higher proportion of apoptotic cells in the area of infiltrates compared to the rest of the intima was associated with a higher proportion of MIB-1-positive cells. Atherosclerotic lesions in diffuse coronary atherosclerosis were advanced, with a predominance of type VII to VIII lesions.