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Genetic and pharmacological inhibition of galectin-3 prevents cardiac remodeling by interfering with myocardial fibrogenesis.
Circ Heart Fail 2013; 6(1):107-17CH

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<0.05 versus control wild type). Galectin-3 knock-out mice also developed LV hypertrophy but without LV dysfunction and fibrosis (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.

Authors+Show Affiliations

Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23230309

Citation

Yu, Lili, et al. "Genetic and Pharmacological Inhibition of Galectin-3 Prevents Cardiac Remodeling By Interfering With Myocardial Fibrogenesis." Circulation. Heart Failure, vol. 6, no. 1, 2013, pp. 107-17.
Yu L, Ruifrok WP, Meissner M, et al. Genetic and pharmacological inhibition of galectin-3 prevents cardiac remodeling by interfering with myocardial fibrogenesis. Circ Heart Fail. 2013;6(1):107-17.
Yu, L., Ruifrok, W. P., Meissner, M., Bos, E. M., van Goor, H., Sanjabi, B., ... de Boer, R. A. (2013). Genetic and pharmacological inhibition of galectin-3 prevents cardiac remodeling by interfering with myocardial fibrogenesis. Circulation. Heart Failure, 6(1), pp. 107-17. doi:10.1161/CIRCHEARTFAILURE.112.971168.
Yu L, et al. Genetic and Pharmacological Inhibition of Galectin-3 Prevents Cardiac Remodeling By Interfering With Myocardial Fibrogenesis. Circ Heart Fail. 2013;6(1):107-17. PubMed PMID: 23230309.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic and pharmacological inhibition of galectin-3 prevents cardiac remodeling by interfering with myocardial fibrogenesis. AU - Yu,Lili, AU - Ruifrok,Willem P T, AU - Meissner,Maxi, AU - Bos,Eelke M, AU - van Goor,Harry, AU - Sanjabi,Bahram, AU - van der Harst,Pim, AU - Pitt,Bertram, AU - Goldstein,Irwin J, AU - Koerts,Jasper A, AU - van Veldhuisen,Dirk J, AU - Bank,Ruud A, AU - van Gilst,Wiek H, AU - Silljé,Herman H W, AU - de Boer,Rudolf A, Y1 - 2012/12/10/ PY - 2012/12/12/entrez PY - 2012/12/12/pubmed PY - 2013/3/6/medline SP - 107 EP - 17 JF - Circulation. Heart failure JO - Circ Heart Fail VL - 6 IS - 1 N2 - 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<0.05 versus control wild type). Galectin-3 knock-out mice also developed LV hypertrophy but without LV dysfunction and fibrosis (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. SN - 1941-3297 UR - https://www.unboundmedicine.com/medline/citation/23230309/Genetic_and_pharmacological_inhibition_of_galectin_3_prevents_cardiac_remodeling_by_interfering_with_myocardial_fibrogenesis_ L2 - http://www.ahajournals.org/doi/full/10.1161/CIRCHEARTFAILURE.112.971168?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -