Genetic and Pharmacological Inhibition of Galectin-3 Prevents Cardiac Remodeling by Interfering With Myocardial Fibrogenesis
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- 1 January 2013
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation: Heart Failure
- Vol. 6 (1), 107-117
- https://doi.org/10.1161/circheartfailure.112.971168
Abstract
Background—: Galectin-3 has been implicated in the development of organ fibrosis. It is unknown whether it is a relevant therapeutic target in cardiac remodeling and heart failure. Methods and Results—: Galectin-3 knock-out and wild-type mice were subjected to angiotensin II infusion (2.5 µg/kg for 14 days) or transverse aortic constriction for 28 days to provoke cardiac remodeling. The efficacy of the galectin-3 inhibitor N-acetyllactosamine was evaluated in TGR(mREN2)27 (REN2) rats and in wild-type mice with the aim of reversing established cardiac remodeling after transverse aortic constriction. In wild-type mice, angiotensin II and transverse aortic constriction perturbations caused left-ventricular (LV) hypertrophy, decreased fractional shortening, and increased LV end-diastolic pressure and fibrosis ( P P =NS). In REN2 rats, pharmacological inhibition of galectin-3 attenuated LV dysfunction and fibrosis. To elucidate the beneficial effects of galectin-3 inhibition on myocardial fibrogenesis, cultured fibroblasts were treated with galectin-3 in the absence or presence of galectin-3 inhibitor. Inhibition of galectin-3 was associated with a downregulation in collagen production (collagen I and III), collagen processing, cleavage, cross-linking, and deposition. Similar results were observed in REN2 rats. Inhibition of galectin-3 also attenuated the progression of cardiac remodeling in a long-term transverse aortic constriction mouse model. Conclusions—: Genetic disruption and pharmacological inhibition of galectin-3 attenuates cardiac fibrosis, LV dysfunction, and subsequent heart failure development. Drugs binding to galectin-3 may be potential therapeutic candidates for the prevention or reversal of heart failure with extensive fibrosis.Keywords
This publication has 34 references indexed in Scilit:
- Modified Citrus Pectin Reduces Galectin-3 Expression and Disease Severity in Experimental Acute Kidney InjuryPLOS ONE, 2011
- Heart failure-associated anemia: bone marrow dysfunction and response to erythropoietinJournal of Molecular Medicine, 2010
- Myeloid mineralocorticoid receptor controls macrophage polarization and cardiovascular hypertrophy and remodeling in miceJCI Insight, 2010
- Galectin‐3, cardiac structure and function, and long‐term mortality in patients with acutely decompensated heart failureEuropean Journal of Heart Failure, 2010
- Prognostic value of galectin-3, a novel marker of fibrosis, in patients with chronic heart failure: data from the DEAL-HF studyClinical Research in Cardiology, 2010
- Intramyocardial Fibroblast Myocyte CommunicationCirculation Research, 2010
- Cardiac FibroblastCirculation Research, 2009
- N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectinAmerican Journal of Physiology-Heart and Circulatory Physiology, 2009
- Measurement of cardiac function using pressure–volume conductance catheter technique in mice and ratsNature Protocols, 2008
- ECM remodeling in hypertensive heart diseaseJCI Insight, 2007