Homeostatic Role of Decorin in Right Ventricular Pressure Overload and Pulmonary Hypertension Induced Remodeling

Yohei Akazawa; Sriram Vaidyanathan; Michael Bradley Dewar; Kana Yazaki; John Dauz; Osami Honjo; Mei Sun; Golam Kabir; Robert P Jankov; Scott Patrick Heximer; Kim A Connelly; Mark K Friedberg

doi:10.1016/j.jacbts.2024.10.007

Homeostatic Role of Decorin in Right Ventricular Pressure Overload and Pulmonary Hypertension Induced Remodeling

JACC Basic Transl Sci. 2025 Mar;10(3):323-341. doi: 10.1016/j.jacbts.2024.10.007. Epub 2024 Dec 18.

Authors

Affiliations

¹ Division of Cardiology, Labatt Family Heart Centre, Hospital for Sick Children, Toronto, Ontario, Canada.
² Department of Pediatrics, Stanford University, Stanford, California, USA.
³ Department of Physiology, University of Toronto, Toronto, Ontario, Canada; Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, University of Toronto, Toronto, Ontario, Canada.
⁴ Division of Cardiology, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada.
⁵ Molecular Biomedicine Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
⁶ Division of Cardiology, Labatt Family Heart Centre, Hospital for Sick Children, Toronto, Ontario, Canada. Electronic address: mark.friedberg@sickkids.ca.

Abstract

Right ventricular (RV) pressure loading induces RV profibrotic signaling and fibrosis associated with RV dysfunction. RV decorin protein levels are decreased in patients with chronic RV pressure loading. RV decorin protein levels are also decreased in 4 animal models of mechanical RV pressure loading and pulmonary arterial hypertension. Human cardiac fibroblasts overexpressing decorin show diminished collagen-1 secretion in response to mechanical or chemical profibrotic stress while decorin knockout human cardiac fibroblasts show increased collagen-1 secretion in response to stress. Downregulation of decorin may play a key role in upregulating transforming growth factor-β1 profibrotic signaling and fibrosis that contribute to RV dysfunction in RV pressure loading.

Keywords: cardiac fibrosis; decorin; pulmonary hypertension; right ventricular dysfunction; right ventricular pressure loading; transforming growth factor-β1.