Focal Adhesion Kinase Drives Rho/ROCK and mTOR Signaling to Protect and Augment Aortic Dissections

Zhen Zhou; Pujun Guan; Ripon Sarkar; Yang Yu; Alexis Richard; Dar Weiss; Yuki Kawamura; Chen Zhang; Yanming Li; Tomas Vaisar; Daniel R Martin; L Maximillian Buja; Zhouxuan Li; Kartik Venkatachalam; Ying H Shen; Scott A LeMaire; Jay D Humphrey; Dianna M Milewicz

doi:10.1016/j.jacbts.2025.101353

Focal Adhesion Kinase Drives Rho/ROCK and mTOR Signaling to Protect and Augment Aortic Dissections

JACC Basic Transl Sci. 2025 Sep;10(9):101353. doi: 10.1016/j.jacbts.2025.101353. Epub 2025 Aug 5.

Authors

Zhen Zhou¹, Pujun Guan¹, Ripon Sarkar¹, Yang Yu², Alexis Richard¹, Dar Weiss³, Yuki Kawamura⁴, Chen Zhang⁵, Yanming Li⁵, Tomas Vaisar⁶, Daniel R Martin⁷, L Maximillian Buja⁸, Zhouxuan Li⁹, Kartik Venkatachalam¹⁰, Ying H Shen⁵, Scott A LeMaire¹¹, Jay D Humphrey¹², Dianna M Milewicz¹³

Affiliations

¹ Division of Medical Genetics, Department of Internal Medicine, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas, USA.
² Division of Medical Genetics, Department of Internal Medicine, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas, USA; Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, China.
³ Department of Biomedical Engineering, Yale University, New Haven, Connecticut, USA; Department of Mechanical Engineering, University of Denver, Denver, Colorado, USA.
⁴ Department of Biomedical Engineering, Yale University, New Haven, Connecticut, USA; School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.
⁵ Department of Surgery, Baylor College of Medicine, Houston, Texas, USA.
⁶ Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, Washington, USA.
⁷ Department of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA.
⁸ Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas, USA.
⁹ Department of Biostatistics and Data Science, The University of Texas Health Science Center at Houston School of Public Health, Houston, Texas, USA.
¹⁰ Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas, USA.
¹¹ Research Institute and Heart & Vascular Institute, Geisinger, Danville, Pennsylvania, USA.
¹² Department of Biomedical Engineering, Yale University, New Haven, Connecticut, USA.
¹³ Division of Medical Genetics, Department of Internal Medicine, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas, USA. Electronic address: dianna.m.milewicz@uth.tmc.edu.

Abstract

Dysfunctional mechanosensing via focal adhesions (FAs) significantly contributes to thoracic aortic dissection in the β-aminopropionitrile mouse model by triggering FA kinase activation and subsequent Rho/ROCK and mTOR signaling pathways. The present findings indicate that these signaling pathways play distinct roles in ascending vs descending dissections. Specifically, in the ascending aorta, smooth muscle cell FA kinase-Rho/ROCK signaling acts as a beneficial adaptive mechanism to prevent dissections, whereas mTOR signaling is pathogenic and contributes to dissections.

Keywords: Rho/ROCK; aortic dissection; extracellular matrix; focal adhesion kinase; lysyl oxidase; mTOR.

Abstract

Grants and funding