Activating PRKG1 Variant Enhances Smooth Muscle Cell Deformability to Cause Aortopathy
Aortic dissection can strike without warning. Whereas the condition is typically linked to aging and chronic hypertension, rare genetic variants emerge as silent culprits. One variant, V219I in PRKG1, has been found in patients with aortic aneurysms despite near-normal aortic diameters. Vascular smooth muscle cells expressing the V219I variant were larger, more deformable, and showed aberrant actin cytoskeleton dynamics. They exhibited altered extracellular matrix signaling and weakened structural integrity, highlighting a shift toward increased tissue elasticity as the causal molecular pathomechanism. These findings offer a mechanistic model for how PRKG1 variants predispose to aortic dissection.
Authors
- Christian Gorzelanny (ORCID: https://orcid.org/0000-0002-3788-6429)
- Giuseppe Melacini (ORCID: https://orcid.org/0000-0003-1164-2853)
- Michaela Schweizer (ORCID: https://orcid.org/0000-0001-5062-328X)
- Bryan VanSchouwen (ORCID: https://orcid.org/0009-0000-6708-7903)
- Markus Matthias Rinschen (ORCID: https://orcid.org/0000-0002-9252-1342)
- Marie Jost
- Meike Rybczynski (ORCID: https://orcid.org/0000-0002-6489-6016)
- Pablo Sáez (ORCID: https://orcid.org/0000-0002-9253-0417)
- Thorsten Stafforst (ORCID: https://orcid.org/0000-0001-9359-3439)
- Laura C. Zelarayán (ORCID: https://orcid.org/0000-0002-9001-0346)
- Mona Brandt
- Ole Pleß (ORCID: https://orcid.org/0000-0002-1468-316X)
- Julia Pflaumenbaum
- Javier Boix-Campos (ORCID: https://orcid.org/0009-0005-2677-165X)
- Anja Billing (ORCID: https://orcid.org/0000-0002-6719-0334)
- Petra Gehle
- Anna Wilsdon
- Friederike Cuello
- Alexandra Fachinger
- Doreen Biedenweg
- Laura Priesmeier
- Oliver Otto
- Johan-Moritz Kux
- Philip Eaton
- Karla Martinez Pomier
- Moritz Lehners
- Shubhangi Singh
- Moyra Schweizer
- Robert Feil
- Philipp Henning
- Rudolph Reimer
- Ulrike Fuchs
- Ruth Newbury-Ecob
- Saskia Siegel
- Till J. Demal
- Viacheslav O. Nikolaev
- Bernhard Ellinger
Institutions
- University of Kassel (DE)
- University of Nottingham (GB)
- Universität Hamburg (DE)
- Queen Mary University of London (GB)
- Aarhus University (DK)
- Universitätsmedizin Greifswald (DE)
- University Hospitals Bristol NHS Foundation Trust (GB)
- Universität Greifswald (DE)
- Deutsches Herzzentrum der Charité (DE)
- Fraunhofer Institute for Translational Medicine and Pharmacology (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- Max Planck Institute for Plasma Physics - Greifswald (DE)
- Universitätsmedizin Göttingen (DE)
- German Centre for Cardiovascular Research (DE)
- William Harvey Research Institute (GB)
- University of Göttingen (DE)
- Charité - Universitätsmedizin Berlin (DE)
- University of Tübingen (DE)
- McMaster University (CA)
Publication Details
- Journal
- JACC Basic to Translational Science
- Published
- 2026-01-15
- DOI
- https://doi.org/10.1016/j.jacbts.2025.101452
- Citations
- 1
- Primary Topic
- Connective tissue disorders research
- Type
- article
- Field-Weighted Citation Impact
- 30.93