PAI-1 deficiency drives pulmonary vascular smooth muscle remodeling and pulmonary hypertension-Reference-Cited by-同舟云学术

PAI-1 deficiency drives pulmonary vascular smooth muscle remodeling and pulmonary hypertension

Published:2024-09-01 Issue:3 Volume:327 Page:L319-L326
ISSN:1040-0605
Container-title:American Journal of Physiology-Lung Cellular and Molecular Physiology
language:en
Short-container-title:American Journal of Physiology-Lung Cellular and Molecular Physiology

Author:

Kudryashova Tatiana V.¹^ORCID,Zaitsev Sergei V.²³,Jiang Lifeng⁴^ORCID,Buckley Benjamin J.⁵,McGuckin Joshua P.⁶,Goncharov Dmitry⁴,Zhyvylo Iryna⁴^ORCID,Lin Derek⁴,Newcomb Geoffrey⁷^ORCID,Piper Bryce⁷,Bogamuwa Srimathi⁷,Saiyed Aisha⁴,Teos Leyla⁴,Pena Andressa¹^ORCID,Ranson Marie⁵^ORCID,Greenland John R.⁸⁹,Wolters Paul J.⁸,Kelso Michael J.⁵,Poncz Mortimer³,DeLisser Horace M.¹⁰,Cines Douglas B.²,Goncharova Elena A.⁴^ORCID,Farkas Laszlo⁷,Stepanova Victoria²^ORCID

Affiliation:

1. University of Pittsburgh Heart, Blood, and Vascular Medicine Institute, Pittsburgh, Pennsylvania, United States

2. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States

3. Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

4. Department of Internal Medicine, University of California, Davis, California, United States

5. School of Chemistry and Molecular Bioscience and Molecular Horizons Institute, University of Wollongong, Wollongong, New South Wales, Australia

6. School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania, United States

7. Division of Pulmonary, Critical Care & Sleep Medicine, Department of Internal Medicine, Davis Heart & Lung Research Institute, The Ohio State University, Columbus, Ohio, United States

8. School of Medicine, University of California, San Francisco, California, United States

9. San Francisco Veterans Affairs Health Care System, San Francisco, California, United States

10. Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Abstract

This study identifies a novel role for the deficiency of plasminogen activator inhibitor (PAI)-1 and resultant unrestricted uPA activity in PASMC remodeling and PH in vitro and in vivo, provides novel mechanistic link from PAI-1 loss through uPA-induced Akt/mTOR and TGFβ-Smad3 upregulation to pulmonary vascular remodeling in PH, and suggests that inhibition of uPA to rebalance the uPA-PAI-1 tandem might provide a novel approach to complement current therapies used to mitigate this pulmonary vascular disease.

Funder

Cardiovascular Medical Research and Education Fund

DHAC | National Health and Medical Research Council

DOD | USA | MEDCOM | MRDC | U.S. Army Medical Research Acquisition Activity

HHS | NIH | National Heart, Lung, and Blood Institute

LAM Foundation

ORD | Clinical Science Research and Development

UCSF | Department of Medicine, University of California, San Francisco

Publisher

American Physiological Society

Link

https://journals.physiology.org/doi/pdf/10.1152/ajplung.00110.2024

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