title: Galectin-3 levels are associated with right ventricular functional and morphologic changes in pulmonary arterial hypertension.
abstract: The response of the right ventricle (RV) to pulmonary arterial hypertension (PAH) involves changes in contractile function, chamber size, hypertrophy, and extracellular matrix (ECM). Galectin-3 (Gal-3) is a mediator of myocardial ECM metabolism and biomarker for left heart remodeling, yet its ability to reflect RV remodeling is unknown. We hypothesized that serum Gal-3 levels correlate with RV morphology and function in PAH, and that Gal-3 is associated with circulating markers of ECM. Fifteen subjects with PAH and 10 age-matched controls underwent same-day echocardiography, cardiac magnetic resonance (CMR) imaging, and phlebotomy for Gal-3 and ECM biomarkers including N-terminal propeptide of type III collagen type (PIIINP), tissue inhibitor of metalloproteinase-1 (TIMP-1), and hyaluronic acid (HA). RV ejection fraction, end diastolic volume index, end systolic volume index, and mass index were calculated using CMR. Echocardiography was used to estimate RV systolic pressure and measure RV strain. Serum Gal-3, TIMP-1, and HA levels were all significantly increased in PAH subjects when compared to controls. Gal-3 correlated with RV ejection fraction (ρ -0.44, p 0.03), end diastolic volume index (ρ 0.42, p 0.03), end systolic volume index (ρ 0.44, p 0.027), mass index (ρ 0.47, p 0.016), systolic pressure (ρ 0.55, p < 0.001), and strain (ρ 0.43, p 0.03). Gal-3 levels positively correlated with the ECM markers TIMP-1 and HA but not with PIIINP. In conclusion, Gal-3 levels are associated with multiple indices of RV function and morphology. Gal-3 may represent a novel biomarker for RV remodeling and associated ECM turnover in PAH.
authors.affiliation: Division of Cardiology, National Jewish Health, 1400 Jackson Street, #J328, Denver, CO, 80206, USA. fensterb@njhealth.org.
authors.forename: Brett E
authors.initials: BE
authors.lastname: Fenster
authors.affiliation: Siemens Healthcare Diagnostics, Tarrytown, NY, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Lasalvia
authors.affiliation: Division of Radiology, National Jewish Health, Denver, CO, USA.
authors.forename: Joyce D
authors.initials: JD
authors.lastname: Schroeder
authors.affiliation: Division of Radiology, National Jewish Health, Denver, CO, USA.
authors.forename: Jamey
authors.initials: J
authors.lastname: Smyser
authors.affiliation: Division of Biostatistics and Bioinformatics, National Jewish Health, Denver, CO, USA.
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Silveira
authors.affiliation: Division of Cardiology, National Jewish Health, 1400 Jackson Street, #J328, Denver, CO, 80206, USA.
authors.forename: J Kern
authors.initials: JK
authors.lastname: Buckner
authors.affiliation: Division of Pulmonary Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Brown
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins; D018619:Echocardiography, Doppler, Pulsed; D005355:Fibrosis; D037502:Galectin 3 / Q000097:blood*; D037161:Galectins; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000097:blood* / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D019028:Magnetic Resonance Imaging, Cine; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods; D010446:Peptide Fragments / Q000097:blood; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011347:Procollagen / Q000097:blood; D011446:Prospective Studies; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D015854:Up-Regulation; D018497:Ventricular Dysfunction, Right / Q000097:blood* / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D016278:Ventricular Function, Right; D017725:Ventricular Pressure; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D037502:Galectin 3; D037161:Galectins; C428445:LGALS3 protein, human; D010446:Peptide Fragments; D011347:Procollagen; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C041876:procollagen Type III-N-terminal peptide; D006820:Hyaluronic Acid
keywords: Biomarker; Cardiac magnetic resonance imaging; Myocardial fibrosis; Pulmonary hypertension; Right ventricle