Activating PRKG1 Variant Enhances Smooth Muscle Cell Deformability to Cause Aortopathy

JACC Basic to Translational Science 2026 Open access

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Authors: Marie 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
+29 more Bryan VanSchouwen, A. 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 Sáez, Oliver Otto, Giuseppe Melacini, T. J. Demal, Thomas Eschenhagen, Friedrich W. Herberg, Friederike Cuello
DOI: 10.1016/j.jacbts.2025.101452
Cited by: 3
References: 72

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.

Fields of Study & Subjects

Connective tissue disorders research Aortic aneurysm repair treatments Aortic Disease and Treatment Approaches

Publication details

Journal / source
JACC Basic to Translational Science
Publisher
Elsevier BV
Volume
11
Issue
2
Pages
101452–101452
Publication date
15 January 2026
Language
EN