TY - GEN A1 - Knaut, M. A1 - Spitzer, Stefan G. A1 - Karolyi, L. A1 - Ebert, H.-H. A1 - Richter, P. A1 - Tugtekin, Sems M. A1 - Schuler, S. T1 - Intraoperative Microwave Ablation for Curative Treatment of Atrial Fibrillation in Open Heart Surgery - The MICRO-STAF and MICRO-PASS Pilot Trial T2 - The thoracic and cardiovascular surgeon N2 - Concomitant microwave ablation for curative treatment of atrial fibrillation (AF) was performed in 18 patients with history of chronic atrial fibrillation and indication for open heart surgery, 11 patients with mitral valve replacement and 7 patients with coronary artery bypass grafting. There were no perioperative complications. During the postoperative period most of the patients had intermittent AF, they received low dose Sotalol therapy and electric cardio-versions. Up to now seven patients have reached follow-up day 90. One patient has persistent AF. Two patients had typical atrial flutter that was electrically converted to sinus rhythm (SR), isthmus ablation is planned. The other four patients have SR, one patient without cardioversions. These four patients show recovered atrial function with observed A-wave for transmitral flow. Under visual guidance the continuous atrial lesion lines could be induced effectively and safely by the intraoperative device Lynx. KW - Atrial fibrillation KW - Intraoperative microwave ablation Y1 - 1999 UR - https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-2007-1013205 U6 - https://doi.org/10.1055/s-2007-1013205 SN - 1439-1902 SN - 0171-6425 VL - 47 IS - Suppl. 3 SP - 379 EP - 384 ER - TY - GEN A1 - Künzel, Stephan R. A1 - Hoffmann, Maximilian A1 - Weber, Silvio A1 - Künzel, Karolina A1 - Kämmerer, Susanne A1 - Günscht, Mario A1 - Klapproth, Erik A1 - Rausch, Johanna S. E. A1 - Sadek, Mirna S. A1 - Kolanowski, Tomasz A1 - Meyer-Roxlau, Stefanie A1 - Piorkowski, Christopher A1 - Tugtekin, Sems M. A1 - Rose-John, Stefan A1 - Yin, Xiaoke A1 - Mayr, Manuel A1 - Kuhlmann, Jan Dominik A1 - Wimberger, Pauline A1 - Grützmann, Konrad A1 - Herzog, Natalie A1 - Küpper, Jan-Heiner A1 - O’Reilly, Molly A1 - Kabir, S. Nashitha A1 - Sommerfeld, Laura C. A1 - Guan, Kaomei A1 - Wielockx, Ben A1 - Fabritz, Larissa A1 - Nattel, Stanley A1 - Ravens, Ursula A1 - Dobrev, Dobromir A1 - Wagner, Michael A1 - El-Armouche, Ali T1 - Diminished PLK2 Induces Cardiac Fibrosis and Promotes Atrial Fibrillation T2 - Circulation Research N2 - Rationale: Fibrosis promotes the maintenance of atrial fibrillation (AF), making it resistant to therapy. Improved understanding of the molecular mechanisms leading to atrial fibrosis will open new pathways toward effective antifibrotic therapies. Objective: This study aims to decipher the mechanistic interplay between PLK2 (polo-like kinase 2) and the profibrotic cytokine OPN (osteopontin) in the pathogenesis of atrial fibrosis and AF. Methods and Results: Atrial PLK2 mRNA expression was 10-fold higher in human fibroblasts than in cardiomyocytes. Compared with sinus rhythm, right atrial appendages and isolated right atrial fibroblasts from patients with AF showed downregulation of PLK2 mRNA and protein, along with increased PLK2 promotor methylation. Genetic deletion as well as pharmacological inhibition of PLK2 induced profibrotic phenotype conversion in cardiac fibroblasts and led to a striking de novo secretion of OPN. Accordingly, PLK2-deficient (PLK2 knockout) mice showed cardiac fibrosis and were prone to experimentally induced AF. In line with these findings, OPN plasma levels were significantly higher only in patients with AF with atrial low-voltage zones (surrogates of fibrosis) compared with sinus rhythm controls. Mechanistically, we identified ERK1/2 as the relevant downstream mediator of PLK2 leading to increased OPN expression. Finally, oral treatment with the clinically available drug mesalazine, known to inhibit ERK1/2, prevented cardiac OPN overexpression and reversed the pathological PLK2 knockout phenotype in PLK2 knockout mice. Conclusions: Abnormal PLK2/ERK1/2/OPN axis function critically contributes to AF-related atrial fibrosis, suggesting reinforcing PLK2 activity and/or OPN inhibition as innovative targets to prevent fibrosis progression in AF. Mesalazine derivatives may be used as lead compounds for the development of novel anti-AF agents targeting fibrosis. KW - atrial fibrillation KW - fibroblasts KW - fibrosis KW - mesalamine KW - osteopontin Y1 - 2021 UR - https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.121.319425 U6 - https://doi.org/10.1161/CIRCRESAHA.121.319425 SN - 1524-4571 SN - 0009-7330 VL - 129 IS - 8 SP - 804 EP - 820 ER -