RESUMO
Telocytes are interstitial cells with long, thin processes by which they contact each other and form a network in the interstitium. Myocardial remodeling of adult patients with different forms of atrial fibrillation (AF) occurs with an increase in fibrosis, age-related isolated atrial amyloidosis (IAA), cardiomyocyte hypertrophy and myolysis. This study aimed to determine the ultrastructural and immunohistochemical features of cardiac telocytes in patients with AF and AF + IAA. IAA associated with accumulation of atrial natriuretic factor was detected in 4.3-25% biopsies of left (LAA) and 21.7-41.7% of right (RAA) atrial appendage myocardium. Telocytes were identified at ultrastructural level more often in AF + IAA, than in AF group and correlated with AF duration and mitral valve regurgitation. Telocytes had ultrastructural signs of synthetic, proliferative, and phagocytic activity. Telocytes corresponded to CD117+, vimentin+, CD34+, CD44+, CD68+, CD16+, S100-, CD105- immunophenotype. No significant differences in telocytes morphology and immunophenotype were found in patients with various forms of AF. CD68-positive cells were detected more often in AF + IAA than AF group. We assume that in aged AF + IAA patients remodeling of atrial myocardium provoked transformation of telocytes into "transitional forms" combining the morphological and immunohistochemical features with signs of fibroblast-, histiocyte- and endotheliocyte-like cells.
Assuntos
Amiloidose/imunologia , Fibrilação Atrial/imunologia , Cardiopatias Congênitas/imunologia , Telócitos/imunologia , Idoso , Amiloidose/complicações , Amiloidose/patologia , Apêndice Atrial/imunologia , Apêndice Atrial/patologia , Fibrilação Atrial/complicações , Fibrilação Atrial/patologia , Feminino , Átrios do Coração/imunologia , Átrios do Coração/patologia , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/patologia , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/imunologia , Insuficiência da Valva Mitral/patologia , Miocárdio/imunologia , Miocárdio/patologia , Telócitos/patologiaRESUMO
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinical practice and is known to be associated with significant morbidity and mortality. Previous studies suggested a link between inflammation and AF by findings of increased inflammatory markers in AF patients. However, it has not been finally clarified whether inflammation is a systemic or a local phenomenon reflecting an active inflammatory process in the heart. To address this subject, human left atrial appendage tissues were obtained from 10 patients who underwent cardiac surgery and subjected to immunohistochemical analysis. The number of inflammatory CD3-positive T cells significantly increased from patients with sinus rhythm to paroxysmal AF and persistent AF, respectively. Interestingly, in patients with persistent AF, these cells were frequently arranged in small clusters. Subsequently, the number of inflammatory CD3-positive T cells decreased and was significantly lower in patients with permanent AF than in patients with persistent AF. Inflammatory CD20-positive B cells could only be detected very occasionally in all AF subgroups and were not locatable in patients with SR. Hence, our data emphasize the potential prominent role of the cellular component of the immune system in the development and perpetuation of AF.
Assuntos
Apêndice Atrial/patologia , Fibrilação Atrial/patologia , Átrios do Coração/patologia , Inflamação/patologia , Idoso , Antígenos CD20/imunologia , Apêndice Atrial/imunologia , Fibrilação Atrial/imunologia , Linfócitos B/imunologia , Complexo CD3/imunologia , Procedimentos Cirúrgicos Cardíacos/métodos , Feminino , Átrios do Coração/imunologia , Humanos , Sistema Imunitário/imunologia , Inflamação/imunologia , Masculino , Linfócitos T/imunologiaRESUMO
Increasing evidence indicates that inflammation contributes to the pathogenesis of atrial fibrillation (AF). Pentraxin 3 (PTX3) is produced abundantly in local inflammatory lesions while C-reactive protein (CRP) is produced mainly in the liver. In this study, we investigated whether a local level of PTX3 might be a sensitive marker for the local inflammation of AF. Blood from the periphery and left atrial appendage (LAA) was sampled from 23 patients with AF undergoing pulmonary vein isolation, and from 10 control subjects with Wolff-Parkinson-White syndrome. We measured peripheral and LAA plasma concentrations of CRP, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and PTX3. Plasma PTX3 concentrations in both locations were higher in patients with AF than in control subjects. PTX3 concentrations were significantly higher in the LAA than the periphery in patients with AF (3.7 ± 1.4 vs 3.3 ± 1.2 ng/ml, P < 0.01), but not in control subjects (2.4 ± 0.5 vs 2.4 ± 0.5 ng/ml, not significant). Patients and controls showed no significant differences in CRP, IL-6, or TNF-α concentrations between the periphery and LAA. Interestingly, there was a significant positive correlation between LAA plasma concentrations of PTX3 and left atrial volume (r = 0.55, P < 0.01). These data demonstrate that local PTX3 production in the left atrium might reflect the local inflammation of AF.
Assuntos
Apêndice Atrial/imunologia , Fibrilação Atrial/imunologia , Proteína C-Reativa/análise , Mediadores da Inflamação/análise , Componente Amiloide P Sérico/análise , Idoso , Fibrilação Atrial/sangue , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Biomarcadores/análise , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Regulação para CimaRESUMO
BACKGROUND: Although clinical studies have suggested a link between inflammation markers and atrial fibrillation (AF), it is still unclear whether local immunologic responses actually exist in human atria during AF. METHODS AND RESULTS: To address this point, human left appendages were obtained from 16 patients who underwent cardiac surgery (5 with sinus rhythm (SR) and 11 with AF) and subjected to immunohistochemical analysis. In all the AF specimens, adhesion and migration of CD45-reactive cells were consistently observed predominantly in the atrial endo- and subendomyocardium and more prominently than in SR. Most of them were immunologically active CD68-positive macrophages, whereas CD3-positive T cells infiltrated to a lesser extent. Scavenger-receptor A staining revealed maturation of macrophages not in the endocardium but in the midmyocardium, a gradient from endo- to midmyocardium. In the endocardium, along with adhesion molecules (intracellular adhesion molecule-1 and vascular cell adhesion molecule-1), a chemotactic protein-1, which facilitates the recruitment, was more abundantly expressed in AF than in SR. Cytokines including transforming growth factor-beta and interleukin-6 were frequently expressed by these macrophages. CONCLUSIONS: These observations collectively imply active adhesion and recruitment of macrophages across the endocardium in human fibrillating atria, thereby supporting the concept of local immunologic inflammatory responses around the atrial endocardium of AF.