Activating PRKG1 Variant Enhances Smooth Muscle Cell Deformability To Cause Aortopathy
Summary
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. Copyright © 2026 The Authors. Published by Elsevier Inc. All rights reserved.
| Authors | Jost ME, Schweizer M, Henning P, Gorzelanny C, Lehners M, Ellinger B, Boix-Campos J, Kux JM, Singh S, Fachinger A, Martinez Pomier K, VanSchouwen B, Billing AM, Biedenweg D, Schweizer M, Siegel S, Reimer R, Brandt M, Priesmeier L, Fuchs U, Pflaumenbaum J, Nikolaev VO, Newbury-Ecob R, Wilsdon A, Rybczynski M, Gehle P, Zelarayán LC, Stafforst T, Feil R, Rinschen MM, Pless O, Eaton P, Sáez PJ, Otto O, Melacini G, Demal TJ, Eschenhagen T, Herberg FW, Cuello F |
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| Journal | JACC. Basic to translational science |
| Publication Date | 2026 Jan 15;11(2):101452 |
| PubMed | 41544301 |
| PubMed Central | PMC12834846 |
| DOI | 10.1016/j.jacbts.2025.101452 |