Andreas Boldt

Bio: Andreas Boldt is an academic researcher from Leipzig University. The author has contributed to research in topics: Medicine & Transplantation. The author has an hindex of 14, co-authored 41 publications receiving 1153 citations. Previous affiliations of Andreas Boldt include Translational Centre for Regenerative Medicine.

Fibrosis in left atrial tissue of patients with atrial fibrillation with and without underlying mitral valve disease

Abstract: Objective: To examine the hypothesis that major extracellular matrix (ECM) proteins are expressed differently in the left atrial tissue of patients in sinus rhythm (SR), lone atrial fibrillation (AF), and AF with underlying mitral valve disease (MVD). Design: Case-control study. Patients: 118 patients with lone AF, MVD+AF, and SR. Main outcome measures: Collagen I, collagen III, and fibronectin protein expression measured by quantitative western blotting techniques and immunohistochemical methods. Results: Protein concentrations increased in patients with AF (all forms) compared with those in SR (all forms): collagen I (1.15 (0.11) v 0.45 (0.28), respectively; p = 0.002), collagen III (0.74 (0.05) v 0.46 (0.11); p = 0.002, and fibronectin (0.88 (0.06) v 0.62 (0.13); p = 0.08). Especially, collagen I was similarly enhanced in both lone AF (1.49 (0.15) and MVD+AF (1.53 (0.16) compared with SR (0.56 (0.28); both p = 0.01). Collagen III was not significantly increased in lone AF but was significantly increased in AF combined with MVD (0.84 (0.07) both compared with SR (0.46 (0.11); p = 0.01). The concentration of fibronectin was not significantly increased in lone AF and MVD+AF (both compared with SR). Furthermore, there was a similar degree of enhanced collagen expression in paroxysmal AF and chronic AF. Conclusions: AF is associated with fibrosis. Forms of AF differ from each other in collagen III expression. However, there was no systematic difference in ECM expression between paroxysmal AF and chronic AF. Enhanced concentrations of ECM proteins may have a role in structural remodelling and the pathogenesis of AF as a result of separation of the cells by fibrotic depositions.

ACE-inhibitor treatment attenuates atrial structural remodeling in patients with lone chronic atrial fibrillation

Abstract: Chronic atrial fibrillation (AF) is characterized by a remodeling process which involves the development of fibrosis. Since angiotensin II has been suspected to be involved in this process, the aim of our study was to investigate a possible influence of an ACE–I therapy in patients with chronic AF regarding the occurrence of left atrial structural remodeling. Atrial tissue samples were obtained from patients with lone chronic AF or sinus rhythm (SR). Collagen I, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) protein expression were measured by quantitative Western Blotting techniques and calculated as mean ± SEM. Histological tissue samples were used for calculating microvessel density (microvessel/mm2 ± SEM). In AF, the collagen amount was higher (1.78 ± 0.21; p = 0.01) vs. SR (0.37 ± 0.07) accompanied by declining microcapillary density (AF: 145 ± 13 vs. SR: 202 ± 9; p = 0.01). Additionally, a negative correlation (p = 0.01) between collagen content and microcapillary density was observed. To investigate the influence of an ACE–I therapy on this remodeling process, patient groups were divided into AF and SR both with or without ACE–I. Interestingly, there was a significantly lower expression of collagen I in AF with ACE–I (1.04 ± 0.26) vs. AF without ACE–I treatment (2.07 ± 0.24, p = 0.02). The microcapillaries were not diminished in AF with ACE–I (180 ± 15) vs. SR with ACE–I (196 ± 9), but there was a significant rarification in AF without ACE–I (123 ± 18; p = 0.03). The expression of VEGF and bFGF did not reveal any significant differences. In patients undergoing ACE–I treatment: atrial structural remodeling was attenuated and the loss of atrial microcapillaries was prevented.

Expression of connexins 40 and 43 in human left atrium in atrial fibrillation of different aetiologies

Abstract: Objective: To test the hypothesis that atrial fibrillation (AF) is associated with changes in the expression of connexins 40 and 43 in the left atrium with more pronounced changes in mitral valve disease than in lone AF. Methods: Protein concentrations of connexin 40 and connexin 43 were analysed in left atrial tissue of patients undergoing cardiac surgery. One group of patients had lone AF (n = 41), one group had AF and mitral valve repair (n = 36), and one group in sinus rhythm served as controls (n = 15). Results: Western blot analysis of connexin 40 and connexin 43 expression showed an increase of both gap junctional proteins (connexin 43 > connexin 40) in patients with AF of all forms compared with patients in sinus rhythm (p = 0.01 and p = 0.011, respectively). Subgroup analysis showed increased concentrations of connexin 40 in lone AF and AF with mitral valve disease compared with sinus rhythm (p = 0.06 and p = 0.029, respectively), whereas the same analysis for connexin 43 reached significance only in the mitral valve disease group (p = 0.031). No differences in connexin 40 and connexin 43 expression were detectable between lone AF and AF with mitral valve disease. Within the groups connexin 40 and connexin 43 expression did not differ between patients with paroxysmal AF and patients with chronic AF. Conclusion: The present study shows for the first time that AF can induce changes in the left atrium with increased connexin expression. Furthermore, no systematic differences between patients with paroxysmal and chronic AF were detected.

Eight‐color immunophenotyping of T‐, B‐, and NK‐cell subpopulations for characterization of chronic immunodeficiencies

Abstract: Background: The heterogeneity of primary and secondary immunodeficiencies demands for the development of a comprehensive flow cytometric screening system, based on reference values that support a standardized immunophenotypic characterization of most lymphocyte subpopulations. Methods: Peripheral blood samples from healthy adult volunteers (n=25) were collected and split into eight panel fractions (100µl each). Subsequently, pre-mixed 8-color antibody cocktails were incubated per specific panel of whole blood to detect and differentiate cell subsets of: (i) a general lymphocyte overviews, (ii) B-cell subpopulations, (iii) CD4+ subpopulations, (iv) CD8+ subpopulations, (v) regulatory T-cells, (vi) recent thymic emigrants, (vii) NK-cell subpopulations, (viii) NK-cell activation markers. All samples were lysed, washed and measured by flow cytometry. FACS DIVA software was used for data analysis and calculation of quadrant statistics (mean values, standard error of mean, percentile ranges). Results: Whole blood staining of lymphocytes provided the analysis of: (i) CD3+, 4+, 8+, 19+, 16/56+, and activated CD4/8 cells; (ii) immature, naive, non-switched/switched, memory, (activated) CD21low , transitional B-cells, plasmablasts/plasmacells; (iii and iv) naive, central memory, effector, effector memory, TH1/TH2/TH17-like and CCR5+CD8-cells; (v) CD25+, regulatory T-cells (naive/memory, HLA-DR+); (vi) α/β- and γ/δ-T-cells, recent thymic emigrants in CD4/CD8 cells; (vii) immature/mature CD56bright , CD94/NKG2D+ NK-cells; and (viii) Nkp30, 44, 46 and CD57+NK-cells. Clinical examples and quadrant statistics are provided. Conclusion: The present study represents a practical approach to standardize the immunophenotyping of most T-, B- and NK-cell subpopulations. That allows differentiating, whether abnormalities or developmental shifts observed in lymphocyte subpopulations originates either from primary or secondary immunological disturbance. © 2014 Clinical Cytometry Society.

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society

Abstract: Jeffrey L. Anderson, MD, FACC, FAHA, Chair Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect Nancy M. Albert, PhD, RN, FAHA Biykem Bozkurt, MD, PhD, FACC, FAHA Ralph G. Brindis, MD, MPH, MACC Mark A. Creager, MD, FACC, FAHA[#][1] Lesley H. Curtis, PhD, FAHA David DeMets, PhD[#][1] Robert A

Pathophysiological Mechanisms of Atrial Fibrillation: A Translational Appraisal

Abstract: Atrial fibrillation (AF) is an arrhythmia that can occur as the result of numerous different pathophysiological processes in the atria. Some aspects of the morphological and electrophysiological al...

Atrial remodeling and atrial fibrillation: mechanisms and implications.

Abstract: Atrial fibrillation (AF) is the most common arrhythmia in clinical practice It can occur at any age but is very rare in children and becomes extremely common in the elderly, with a prevalence approaching 20% in patients >85 years of age1 AF is associated with a wide range of potential complications and contributes significantly to population morbidity and mortality Present therapeutic approaches to AF have major limitations, including limited efficacy and significant adverse effect liability These limitations have inspired substantial efforts to improve our understanding of the mechanisms underlying AF, with the premise that improved mechanistic insights will lead to innovative and improved therapeutic approaches2 Our understanding of AF pathophysiology has advanced significantly over the past 10 to 15 years through an increased awareness of the role of “atrial remodeling” Any persistent change in atrial structure or function constitutes atrial remodeling Many forms of atrial remodeling promote the occurrence or maintenance of AF by acting on the fundamental arrhythmia mechanisms illustrated in Figure 1 Both rapid ectopic firing and reentry can maintain AF Reentry requires a suitable vulnerable substrate, as well as a trigger that acts on the substrate to initiate reentry Ectopic firing contributes to reentry by providing triggers for reentry induction Atrial remodeling has the potential to increase the likelihood of ectopic or reentrant activity through a multitude of potential mechanisms This article reviews the types of atrial remodeling, their underlying pathophysiology, the molecular basis of their occurrence, and finally, their potential therapeutic significance Figure 1 General schema representing AF mechanisms and the role of remodeling The mechanisms underlying AF are portrayed schematically in Figure 2 AF can be maintained by rapid focal firing, which may itself be regular but result in fibrillatory activity because of wave breakup in portions of the atrium that …