Jun Yang, Anjira S. Ambade, Melanie Nies, Megan Griffiths, Rachel Damico, Dhananjay Vaidya, Stephanie Brandal, Michael W. Pauciulo, Katie A. Lutz, Anna W. Coleman, William C. Nichols, Eric D. Austin, Dunbar Ivy, Paul M. Hassoun, Allen D. Everett
Johns Hopkins University. Vagelos College of Physicians and Surgeons Columbia University. University of Cincinnati College of Medicine and Children’s Hospital Medical Center. Vanderbilt University Medical Center. Children’s Hospital Colorado and University of Colorado.
United States
Pulmonary Circulation
Pulm Circ 2022; 12:
DOI: 10.1002/pul2.12007
Abstract
Hepatoma-derived growth factor (HDGF) was previously shown to be associated with increased mortality in a small study of idiopathic and connective tissue disease-associated pulmonary arterial hypertension (PAH). In this study, we measured serum HDGF levels in a large multicenter cohort (total 2017 adult PAH-Biobank enrollees), we analyzed the associations between HDGF levels and various clinical measures using linear or logistic regression models. Higher HDGF levels were found to be significantly associated with worse pulmonary hemodynamics, prostacyclin treatment; among PAH subtypes, higher HDGF levels were most associated with portopulmonary hypertension (beta = 0.469, p < 0.0001). Both Kaplan-Meier curve and Cox proportional hazard regression demonstrated that higher HDGF levels are associated with a higher risk of mortality (COX hazard ratio 1.31, p < 0.0001). Further, in the Sugen hypoxia (SuHx) rat model, the highest HDGF levels were post-pulmonary circulation, and HDGF levels significantly increased with the development of PAH. In pulmonary arteries, immunohistochemistry staining showed that HDGF was highly expressed in pulmonary smooth muscle cells in both PAH patients and SuHx rats. In conclusion, we found that higher serum HDGF was linked with increased mortality, and associated with disease severity in a large multi-center adult PAH cohort (n = 2017). In the SuHX PAH models, circulating HDGF levels are pulmonary in origin and increase with PAH progression. HDGF may be actively involved in vascular remodeling in PAH.
Category
Acquired Patient Factors Associated with Pulmonary Vascular Disease
Potential Biomarkers Associated with Pulmonary Vascular Disease
Animal Models of Pulmonary Vascular Disease and Therapy
Age Focus: Adult Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes