Galectin-3 Expression in the Left Ventricular Interstitium of Dogs with Chronic Heart Failure: Association with Interstitial Fibrosis.
Sabbah HN, Singh-Gupta V, and Gupta RC. Galectin-3 Expression in the Left Ventricular Interstitium of Dogs with Chronic Heart Failure: Association with Interstitial Fibrosis. J Heart Lung Transplant 2019; 38(4 Suppl ):S247.
J Heart Lung Transplant
Purpose: Accumulation of collagen in the cardiac interstitium termed “reactive interstitial fibrosis (RIF)” occurs in heart failure (HF) with reduced ejection fraction (HFrEF) as well as in HF with preserved EF (HFpEF). This maladaptation leads to increased myocardial stiffness that negatively impacts ventricular filling. RIF also results in poor oxygen diffusion between capillaries and cardiomyocytes leading to cardiomyocyte hypoxia that promotes cellular contractile dysfunction and triggers programmed cell death. The protein galectin-3 (GAL-3) is a member of the lectin family. Increased expression of GAL-3 is implicated in the development of fibrosis in multiple organs including the heart. Elevated levels of GAL-3 are significantly associated with higher risk of death in patients with HF. In this study, we examined whether increased expression of GAL-3 occurs in the LV interstitium of dogs with chronic HF that also manifest increased levels of RIF. Methods: Studies were performed in LV tissue obtained from 7 normal (NL) dogs and 7 dogs with coronary microembolization-induced HF. Frozen LV sections, 6 µm in thickness, were used for fluorescence immunostaining with antibodies against myosin heavy chain and GAL-3. DAPI (4′ 6-diamidino-2-phenylindole) was used to stain nuclei. Confocal images of stained sections were obtained with an Olympus Fluoview FV1000 laser scanning biological microscope. From each section, 4-6 fields, each ∼10 mm2, were randomly selected for laser scanning and subsequently used to calculate the percent area occupied by GAL-3 (%aGAL-3) from each field. The percent area occupied by RIF (%aRIF) was also calculated using frozen sections stained with fluorescein-labeled peanut agglutinin. Results: In NL dogs, the %aRIF was 3.70 ± 0.07 and %aGAL-3 was 2.40 ± 0.45. In dogs with HF, the %aRIF increased significantly to 13.5 ± 0.57 (p<0.05) and the %aGAL-3 increased significantly to 12.82 ± 1.15 (p<0.05). Conclusion: The results indicate that in dogs with HF, increased levels of RIF is associated with increased interstitial levels of GAL-3. The findings support the use of this dog model of HF to evaluate the effects of GAL-3 inhibitors for preventing or attenuating RIF that develops during the evolution of HF.