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Genetic and Pharmacological Inhibition of Galectin-3 Prevents Cardiac Remodeling by Interfering With Myocardial Fibrogenesis
Study Questions:
Is galectin-3, implicated in organ fibrosis, a potential therapeutic target in heart failure (HF)?
Methods:
Wild type (WT) and galectin-3 knock-out mice were subjected to angiotensin II (AGII) infusions for 14 days or transverse aortic constriction (TAC) for 28 days, and morphologic changes were observed. In a separate study, WT mice and TGR (mREN2)27 (REN2) rats with experimental HF were then given N-acetyllactosamine, a galactin-3 inhibitor (Gal3-I). Changes in ventricular morphology, systolic and diastolic function, and fibrosis were compared.
Results:
WT and galectin-3 knock-out mice developed left ventricular (LV) hypertrophy with TAC or AGII, but only WT mice developed LV systolic and diastolic dysfunction and fibrosis. Galectin-3 was only elevated in WT mice. In REN2 rats with HF, inhibition of galectin-3 with Gal3-I led to less LV dysfunction and fibrosis than that of untreated REN2 rats with HF. Inhibition of galactin-3 with Gal3-I in cultured fibroblasts led to less collagen production and less collagen turnover.
Conclusions:
The authors concluded that in animal models, inhibition of galectin-3 attenuates fibrosis and LV dysfunction.
Perspective:
Systolic and diastolic HF are associated with adverse myocardial remodeling and fibrosis. Many mediators of myocardial fibrosis have been identified, including the renin-angiotensin-aldosterone system and sympathetic nervous system. Angiotensin-converting enzyme inhibitors, aldosterone antagonists, and beta-blockers are thought to reduce remodeling through impact on these fibrosis-mediators. In this study, galectin-3 appears to play an instigatory role in myocardial fibrosis in murine animals. It is hopeful that similar improvements in myocardial remodeling can be seen in human study.
Keywords: Constriction, Ventricular Dysfunction, Fibroblasts, Mineralocorticoid Receptor Antagonists, Renin-Angiotensin System, Galectin 3, Systole, Biomarkers, Sympathetic Nervous System, Ventricular Remodeling, Heart Failure, Hypertrophy, Collagen, Diastole, Fibrosis
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