Carly E. Byrd, Jennifer E. Schramm, Jun Yang, Allan E. Barnes, Megan Griffiths, Anjira S. Ambade, Darin T. Rosen, Ilton M. Cubero Salazar, Catherine E. Simpson, Ryan J. Tedford, Steven Hsu, Dhananjay Vaidya, Todd M. Kolb, Michael W. Pauciulo, William C. Nichols, David D. Ivy, Eric D. Austin, Paul M. Hassoun, Rachel L. Damico, Allen D. Everett
Johns Hopkins University. University of Texas Southwestern Medical Center. Medical University of South Carolina. Cincinnati Children’s Hospital Medical Center andUniversity of Cincinnati College of Medicine. Children’s Hospital Colorado. Vanderbilt University Medical Center. University of Miami.
United States
Pulmonary Circulation
Pulm Circ 2025; 15:
DOI: 10.1002/pul2.70067
Abstract
Cellular communication network 2 (CCN2) is a secreted matricellular protein associated with pulmonary arterial hypertension (PAH) but has not been studied relative to PAH severity, outcomes, or right ventricle (RV) structure and function in a large human cohort and preclinical animal model. This study assessed the associations between CCN2 and PAH severity, survival, hemodynamic measurements, and cardiovascular dysfunction. Serum CCN2 levels were compared in 2548 adults with PAH and 216 controls. CCN2 levels in PAH patients were compared to functional and hemodynamic measurements, and survival outcomes. RV-pulmonary artery coupling and RV morphology were also assessed in a small subset of patients via pressure-volume loops and cardiac magnetic resonance imaging. In a preclinical PAH model, plasma CCN2 levels were compared between ventricles with PAH progression. CCN2 mRNA levels in both ventricles in the preclinical model were measured to compare with morphologic histologic variables. CCN2 serum levels were significantly higher in PAH compared to controls (p < 0.0001). Higher CCN2 levels were associated with reduced RV contractility (p = 0.003). Higher CCN2 levels were associated with worse 6MWD (p = 0.035), and higher risk of mortality or transplant (p = 0.025). In the preclinical model, prepulmonary CCN2 plasma levels increased with the progression of disease. CCN2 mRNA levels in the RV were associated with decreased RV capillary density (p = 0.015) and increased RV fibrosis (p = 0.045). Though more investigation is needed, it appears that CCN2 plays a role in the development of PAH and potentially in RV maladaptation in PAH.
Category
Right Heart Dysfunction Associated with Pulmonary Vascular Disease
Diagnostic Testing for Pulmonary Vascular Disease. Risk Stratification
Potential Biomarkers Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease or Adult Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes