1. Academic Validation
  2. Strong Signs for a Weak Wall in Tricuspid Aortic Valve Associated Aneurysms and a Role for Osteopontin in Bicuspid Aortic Valve Associated Aneurysms

Strong Signs for a Weak Wall in Tricuspid Aortic Valve Associated Aneurysms and a Role for Osteopontin in Bicuspid Aortic Valve Associated Aneurysms

  • Int J Mol Sci. 2019 Sep 26;20(19):4782. doi: 10.3390/ijms20194782.
Christian Stern 1 2 Bernhard Scharinger 3 4 Adrian Tuerkcan 5 Clemens Nebert 6 Teresa Mimler 7 Ulrike Baranyi 8 Christian Doppler 9 10 Thomas Aschacher 11 12 Martin Andreas 13 Marie-Elisabeth Stelzmueller 14 Marek Ehrlich 15 Alexandra Graf 16 Guenther Laufer 17 David Bernhard 18 19 Barbara Messner 20
Affiliations

Affiliations

  • 1 Cardiac Surgery Research Laboratory, Department of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria. Christian.stern@medizin.uni-halle.de.
  • 2 Julius-Bernstein-Institute for Physiology, Medical Faculty of the Martin-Luther- University, 06112 Halle-Wittenberg, Germany. Christian.stern@medizin.uni-halle.de.
  • 3 Cardiac Surgery Research Laboratory, Department of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria. be.scharinger@salk.at.
  • 4 Department of Radiology, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria. be.scharinger@salk.at.
  • 5 Cardiac Surgery Research Laboratory, Department of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria. atuerkcan@gmail.com.
  • 6 Cardiac Surgery Research Laboratory, Department of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria. clemens.nebert@meduniwien.ac.at.
  • 7 Cardiac Surgery Research Laboratory, Department of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria. teresa.mimler@meduniwien.ac.at.
  • 8 Cardiac Surgery Research Laboratory, Department of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria. ulrike.baranyi@meduniwien.ac.at.
  • 9 Cardiac Surgery Research Laboratory, University Clinic for Cardiac Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria. christian.doppler@jku.at.
  • 10 Division for Pathophysiology, Institute of Physiology and Pathophysiology, Johannes Kepler University Linz, 4020 Linz, Austria. christian.doppler@jku.at.
  • 11 Cardiac Surgery Research Laboratory, Department of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria. thomas.aschacher@meduniwien.ac.at.
  • 12 Department of Surgery, Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria. thomas.aschacher@meduniwien.ac.at.
  • 13 Department of Surgery, Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria. martin.andreas@meduniwien.ac.at.
  • 14 Department of Surgery, Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria. marie-elisabeth.stelzmueller@meduniwien.ac.at.
  • 15 Department of Surgery, Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria. marek.ehrlich@meduniwien.ac.at.
  • 16 Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, 1090 Vienna, Austria. alexandra.graf@meduniwien.ac.at.
  • 17 Department of Surgery, Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria. guenther.laufer@meduniwien.ac.at.
  • 18 Cardiac Surgery Research Laboratory, University Clinic for Cardiac Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria. david.bernhard@jku.at.
  • 19 Division for Pathophysiology, Institute of Physiology and Pathophysiology, Johannes Kepler University Linz, 4020 Linz, Austria. david.bernhard@jku.at.
  • 20 Cardiac Surgery Research Laboratory, Department of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria. barbara.messner@meduniwien.ac.at.
Abstract

Central processes in the pathogenesis of TAV- (tricuspid aortic valve) and BAV- (bicuspid aortic valve) associated ascending thoracic aortic aneurysm (ATAA) development are still unknown. To gain new insights, we have collected aortic tissue and isolated smooth muscle cells of aneurysmal tissue and subjected them to in situ and in vitro analyses. We analyzed aortic tissue from 78 patients (31 controls, 28 TAV-ATAAs, and 19 BAV-ATAAs) and established 30 primary smooth muscle cell cultures. Analyses included histochemistry, immuno-, auto-fluorescence-based image analyses, and cellular analyses including smooth muscle cell contraction studies. With regard to TAV associated aneurysms, we observed a strong impairment of the vascular wall, which appears on different levels-structure and dimension of the layers (reduced media thickness, increased intima thickness, atherosclerotic changes, degeneration of aortic media, decrease of collagen, and increase of elastic fiber free area) as well as on the cellular level (accumulation of fibroblasts/myofibroblasts, and increase in the number of smooth muscle cells with a reduced alpha smooth muscle actin (α-SM actin) content per cell). The pathological changes in the aortic wall of BAV patients were much less pronounced-apart from an increased expression of osteopontin (OPN) in the vascular wall which stem from smooth muscle cells, we observed a trend towards increased calcification of the aortic wall (increase significantly associated with age). These observations provide strong evidence for different pathological processes and different disease mechanisms to occur in BAV- and TAV-associated aneurysms.

Keywords

alpha smooth muscle actin; atherosclerosis; bicuspid; focal elastic fiber loss; osteopontin; tricuspid.

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