Diminished PLK2 Induces Cardiac Fibrosis and Promotes Atrial Fibrillation

Stephan R Künzel; Maximilian Hoffmann; Silvio Weber; Karolina Künzel; Susanne Kämmerer; Mario Günscht; Erik Klapproth; Johanna S E Rausch; Mirna S Sadek; Tomasz Kolanowski; Stefanie Meyer-Roxlau; Christopher Piorkowski; Sems M Tugtekin; Stefan Rose-John; Xiaoke Yin; Manuel Mayr; Jan Dominik Kuhlmann; Pauline Wimberger; Konrad Grützmann; Natalie Herzog; Jan-Heiner Küpper; Molly O'Reilly; S Nashitha Kabir; Laura C Sommerfeld; Kaomei Guan; Ben Wielockx; Larissa Fabritz; Stanley Nattel; Ursula Ravens; Dobromir Dobrev; Michael Wagner; Ali El-Armouche

doi:10.1161/CIRCRESAHA.121.319425

Diminished PLK2 Induces Cardiac Fibrosis and Promotes Atrial Fibrillation

Circ Res. 2021 Oct;129(8):804-820. doi: 10.1161/CIRCRESAHA.121.319425. Epub 2021 Aug 26.

Authors

Stephan R Künzel^#^{1

2}, Maximilian Hoffmann^#¹, Silvio Weber¹, Karolina Künzel¹, Susanne Kämmerer¹, Mario Günscht¹, Erik Klapproth¹, Johanna S E Rausch¹, Mirna S Sadek¹, Tomasz Kolanowski¹, Stefanie Meyer-Roxlau¹, Christopher Piorkowski³, Sems M Tugtekin⁴, Stefan Rose-John⁵, Xiaoke Yin⁶, Manuel Mayr^{6

7}, Jan Dominik Kuhlmann^{8

9

10}, Pauline Wimberger^{8

9

10}, Konrad Grützmann^{1

10}, Natalie Herzog¹¹, Jan-Heiner Küpper¹¹, Molly O'Reilly¹², S Nashitha Kabir¹², Laura C Sommerfeld^{12

13}, Kaomei Guan, Ben Wielockx¹⁴, Larissa Fabritz^{15

13}, Stanley Nattel^{16

17

18}, Ursula Ravens¹⁹, Dobromir Dobrev^{16

17

20}, Michael Wagner^#^{1

3}, Ali El-Armouche^#¹

Affiliations

¹ Institute of Pharmacology and Toxicology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden (S.R.K., M.H., S.W., K.K., S.K., M.G., E.K., J.S.E.R., M.S.S., T.K., S.M.-R., K.G., M.W., A.E.-A.).
² Department of Dermatology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden (S.R.K.).
³ Department of Rhythmology (C.P., M.W.), Clinic for Internal Medicine and Cardiology, Heart Center Dresden GmbH, Dresden, Technische Universität Dresden.
⁴ Department of Cardiac Surgery (S.M.T.), Clinic for Internal Medicine and Cardiology, Heart Center Dresden GmbH, Dresden, Technische Universität Dresden.
⁵ Unit for Degradomics of the Protease Web, Institute of Biochemistry, University of Kiel (S.R.-J.).
⁶ The James Black Centre, King's College, University of London (X.Y., M.M.).
⁷ Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden (M.M.).
⁸ Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden (J.D.K., P.W.).
⁹ German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg (J.D.K., P.W.).
¹⁰ National Center for Tumor Diseases (NCT), Partner Site Dresden (J.D.K., P.W., K.G.).
¹¹ Brandenburg University of Technology, Senftenberg (N.H., J.-H.K.).
¹² Institute of Cardiovascular Sciences, University of Birmingham (M.O., S.N.K., L.C.S.).
¹³ University Center of Cardiovascular Science and Department of Cardiology, University Heart and Vascular Center Hamburg (L.F., L.C.S.).
¹⁴ Institute of Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden (B.W.).
¹⁵ Department of Cardiology, University Hospitals Birmingham (L.F.).
¹⁶ Department of Medicine, Montreal Heart Institute and Université de Montréal, Quebec, Canada (S.N., D.D.).
¹⁷ Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen (S.N., D.D.).
¹⁸ IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université (S.N.).
¹⁹ Institut für Experimentelle Kardiovaskuläre Medizin, Universitäts Herzzentrum, Freiburg Bad Krotzingen, Freiburg im Breisgau (U.R.).
²⁰ Department of Molecular Physiology and Biophysics, Baylor College of Medicine (D.D.).

^# Contributed equally.

Abstract

[Figure: see text].

Keywords: atrial fibrillation; fibroblasts; fibrosis; mesalamine; osteopontin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Animals
Atrial Fibrillation / drug therapy
Atrial Fibrillation / genetics
Atrial Fibrillation / metabolism*
Atrial Fibrillation / pathology
Cells, Cultured
Female
Fibrosis
Humans
Male
Mesalamine / pharmacology
Mesalamine / therapeutic use
Mice
Mice, Inbred C57BL
Middle Aged
Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
Mitogen-Activated Protein Kinase 3 / metabolism
Myocardium / metabolism*
Myocardium / pathology
Myofibroblasts / drug effects
Myofibroblasts / metabolism
Myofibroblasts / pathology
Osteopontin / metabolism
Protein Kinase Inhibitors / pharmacology
Protein Kinase Inhibitors / therapeutic use
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism*

Substances

Protein Kinase Inhibitors
Osteopontin
Mesalamine
PLK2 protein, human
Protein Serine-Threonine Kinases
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3

Abstract

Publication types

MeSH terms

Substances

Grants and funding