Published May 8, 2024 | Version v1
Journal Article Open

Bioengineered vascular grafts with a pathogenic TGFBR1 variant model aneurysm formation in vivo and reveal underlying collagen defects

Creators

  • 1. ROR icon University of Michigan
  • 2. ROR icon Second Xiangya Hospital of Central South University

Description

Thoracic aortic aneurysms (TAAs) form in patients with Loeys-Dietz syndrome (LDS), but in vivo models that recapitulate the pathophysiological features of early human disease are limited. Here, Yang and colleagues generated bioengineered vascular grafts using vascular smooth muscle cells (SMCs) derived from human induced pluripotent stem cells and implanted them into the common carotid arteries of nude rats to model TAA. Grafts seeded with cells containing a pathogenic variant in TGFBR1, which causes LDS, were shown to dilate in the face of strain caused by blood flow, and the authors found lower expression of collagen-related genes and impaired prolyl hydroxylase activity in uncorrected LDS grafts, suggesting that specific deficiencies in the extracellular matrix contribute to TAA formation in this disease. 

Acknowledgements

We are grateful to K. Converso-Baran of University of Michigan Frankel Cardiovascular Center and Department of Molecular & Integrative Physiology Phenotyping Core for ultrasound test and analysis and K. Poli of Mechanical Engineering for mechanical test and analysis. We also thank the University of Michigan Advanced Genomics Core for performing spatial transcriptomics profiling of vascular grafts.

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Additional details

Funding

National Heart Lung and Blood Institute
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