Abstract 12433: Plasma Galectin-3 Levels in Patients with Structural and Clinical Manifestations of Hypertensive Heart Disease: Relationship to Determinants of Matrix Composition

Background: The β-galactoside binding protein galectin-3 (Gal-3) has been demonstrated to regulate both cellular and extracellular structure and function in tissue remodeling processes such as inflammation and cancer. Gal-3 binds to a number of extracellular matrix (ECM) ligands including fibrillar collagens, basement membrane proteins and integrins. The development of LV hypertrophy (LVH) and progression to diastolic heart failure (DHF) are accompanied by significant changes in the ECM, but whether plasma Gal-3 levels are altered in these processes and related to other determinants of ECM remodeling is unknown. Methods/Results: Plasma profiles for Gal-3 and determinants of ECM remodeling such as matrix metalloproteinases (MMPs-2,-9,-3,-7,-8), tissue inhibitors of MMPs (TIMPs-1,-2,-3,-4), and collagen peptides (PIIINP, CITP) were measured by high sensitivity immunoassays in control subjects (n=19 CTL); patients with LVH but no DHF (n=21, LVH), and patients with LVH and DHF (n=21, DHF). Echocardiography and 6 minute hall walk (6MHW) showed that DHF patients had shorter 6MHW and increased pulmonary wedge pressures vs. CTL or LVH. Plasma MMP-2, TIMP-1, TIMP-4, NT-proBNP, and Gal-3 were increased in the DHF group vs. CTL and LVH, (Table). Gal-3 values were significantly correlated with changes in MMP-2, TIMP-1, TIMP-4, and NT-proBNP (all r ≥0.3, p Conclusions: Plasma profiles of the bioactive molecule Gal-3, which regulates ECM composition and structure, were significantly increased in patients with DHF; Gal-3 was associated with changes in other determinants of ECM remodeling. Thus, biomarker profiling of the ECM remodeling process holds potential diagnostic and prognostic utility in identifying patients transitioning from LVH to DHF.