2. Academic Validation
  3. Non-canonical atherosclerosis as the driving force in tricuspid aortic valve associated aneurysms - a trace collection

Non-canonical atherosclerosis as the driving force in tricuspid aortic valve associated aneurysms - a trace collection

  • J Lipid Res. 2023 Jan 31;100338. doi: 10.1016/j.jlr.2023.100338.
Christian Doppler 1,  Barbara Messner 2,  Teresa Mimler 3,  Bruno Schachner 4,  Marlene Rezk 5,  Clara Ganhör 1,  Christian Wechselberger 1,  Marina Müller 1,  Spela Puh 1,  Johannes Pröll 6,  Barbara Arbeithuber 5,  Thomas Müller 7,  Andreas Zierer 4,  David Bernhard 8
Affiliations

Affiliations

  • 1 Division of Pathophysiology, Institute of Physiology and Pathophysiology, Medical Faculty, Johannes Kepler University Linz, Linz, Austria.
  • 2 Department of Cardiac Surgery, Cardiac Surgery Research Laboratory, Medical University of Vienna, Vienna, Austria.
  • 3 Division of Pathophysiology, Institute of Physiology and Pathophysiology, Medical Faculty, Johannes Kepler University Linz, Linz, Austria; Department of Cardiac Surgery, Cardiac Surgery Research Laboratory, Medical University of Vienna, Vienna, Austria.
  • 4 Department of Cardiothoracic and Vascular Surgery, Kepler University Hospital, Medical Faculty, Johannes Kepler University Linz, Linz, Austria.
  • 5 Experimental Gynecology, Obstetrics and Gynecological Endocrinology, Kepler University Hospital Linz, Johannes Kepler University Linz, Linz, Austria.
  • 6 Center for Medical Research, Medical Faculty, Johannes Kepler University Linz, Linz, Austria.
  • 7 Institute of Organic Chemistry, Faculty of Natural Sciences, Leopold-Franzens University Innsbruck, Innsbruck, Austria.
  • 8 Division of Pathophysiology, Institute of Physiology and Pathophysiology, Medical Faculty, Johannes Kepler University Linz, Linz, Austria; Center for Medical Research, Medical Faculty, Johannes Kepler University Linz, Linz, Austria. Electronic address: david.bernhard@jku.at.
PMID: 36736622 DOI: 10.1016/j.jlr.2023.100338
Abstract

Pathogenic mechanisms in degenerative thoracic aortic aneurysms (TAA) are still unclear. There is an ongoing debate about whether TAAs are caused by uniform or distinct processes, which would obviously have a major impact on future treatment strategies. Clearly, the ultimate outcome of TAA subgroups associated with a tricuspid aortic valve (TAV) or a bicuspid aortic valve (BAV) is the same, namely a TAA. Based on results from our own and others' studies, we decided to compare the different TAAs (TAV and BAV) and controls using a broad array of analyses, i.e. metabolomic analyses, gene expression profiling, protein expression analyses, histological characterization, and MALDI imaging. Central findings of the present study are the presence of non-canonical atherosclerosis, pathological accumulation of macrophages and disturbances of lipid metabolism in the aortic media. Moreover, we have also found that lipid metabolism is impaired systemically. Importantly, all of the above described phenotypes are characteristic for TAV-TAA only, and not for BAV-TAA. In summary, our results suggest different modes of pathogenesis in TAV- and BAV-associated aneurysms. Intimal atherosclerotic changes play a more central role in TAV-TAA formation than previously thought, particularly as the observed alterations do not follow classical patterns. Atherosclerotic alterations are not limited to the intima, but also affect and alter the TAV-TAAs media. Further studies are needed to i) clarify patho-relevant intima-media interconnections, ii) define the origin of the systemic alteration of lipid metabolism, and iii) to define valid biomarkers for early diagnosis, disease progression and successful treatments in TAV-TAAs.

Keywords

Lipidomics; cholesterol; lysophosphatidylcholine; matrix-assisted laser desorption ionization mass spectrometry; smooth muscle cells.

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