Homeostatic Role of Decorin in Right Ventricular Pressure Overload and Pulmonary Hypertension Induced Remodeling
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.
Authors
- Robert P. Jankov (ORCID: https://orcid.org/0000-0002-9095-4398)
- Kana Yazaki (ORCID: https://orcid.org/0000-0003-3546-481X)
- Osami Honjo (ORCID: https://orcid.org/0000-0002-6373-0532)
- Michael Bradley Dewar (ORCID: https://orcid.org/0000-0003-1913-0991)
- John Dauz
- Golam Kabir
- Yohei Akazawa
- Kim A. Connelly (ORCID: https://orcid.org/0000-0002-1031-3137)
- Sriram Vaidyanathan (ORCID: https://orcid.org/0000-0001-9167-3056)
- Mark K. Friedberg (ORCID: https://orcid.org/0000-0002-4108-5560)
- Scott P. Heximer (ORCID: https://orcid.org/0000-0001-5489-9240)
- Mei Sun (ORCID: https://orcid.org/0000-0003-4138-4699)
Institutions
- St. Michael's Hospital (CA)
- Children's Hospital of Eastern Ontario (CA)
- Hospital for Sick Children (CA)
- Ted Rogers Centre for Heart Research (CA)
- SickKids Foundation (CA)
- Stanford University (US)
Publication Details
- Journal
- JACC Basic to Translational Science
- Published
- 2024-12-18
- DOI
- https://doi.org/10.1016/j.jacbts.2024.10.007
- Citations
- 3
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 0.70
Funders
- Heart and Stroke Foundation of Canada
- Canadian Institutes of Health Research