Activating PRKG1 Variant Enhances Smooth Muscle Cell Deformability to Cause Aortopathy
Year: 2026
Type: article
Abstract: 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: Marie E. Jost, Moyra Schweizer, Moyra Schweizer, Philipp Henning, Christian Gorzelanny, Moritz Lehners, Bernhard Ellinger, Javier Boix-Campos, Johan-Moritz Kux, Shubhangi Singh, Alexandra Fachinger, Karla Martinez Pomier, Bryan VanSchouwen, Anja M. Billing, Doreen Biedenweg, Michaela Schweizer, Michaela Schweizer, Saskia Siegel, Rudolph Reimer, Mona Brandt, Laura Priesmeier, Ulrike Fuchs, Julia Pflaumenbaum, Viacheslav O. Nikolaev, Ruth Newbury-Ecob, Anna Wilsdon, Meike Rybczynski, Petra Gehle, Laura C. Zelarayán, Thorsten Stafforst, Robert Feil, Markus M. Rinschen, Ole Pless, Philip Eaton, Pablo J. Sáez, Oliver Otto, Giuseppe Melacini, Till J. Demal, Thomas Eschenhagen, Friedrich W. Herberg, Friederike Cuello
Institutions: University Medical Center Hamburg-Eppendorf, University of Kassel, University of Tübingen, Fraunhofer Institute for Translational Medicine and Pharmacology, McMaster University, Aarhus University, Universität Greifswald, Leibniz Institute of Virology (LIV), Universitätsmedizin Göttingen, University of Göttingen, Universität Hamburg, German Centre for Cardiovascular Research, University Hospitals Bristol NHS Foundation Trust, University of Nottingham, Deutsches Herzzentrum der Charité, Justus-Liebig-Universität Gießen, Queen Mary University of London
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,750
Award: G3724418959
OpenAlex ID: W7124417594