Pectins from various sources inhibit galectin-3-related cardiac fibrosis

Carolin Pozder Geb Gehlken; A Rogier van der Velde; Wouter C Meijers; Herman H W Silljé; Pieter Muntendam; Martin M Dokter; Wiek H van Gilst; Henk A Schols; Rudolf A de Boer

doi:10.1016/j.retram.2021.103321

Pectins from various sources inhibit galectin-3-related cardiac fibrosis

Curr Res Transl Med. 2022 Jan;70(1):103321. doi: 10.1016/j.retram.2021.103321. Epub 2021 Nov 23.

Authors

Carolin Pozder Geb Gehlken¹, A Rogier van der Velde¹, Wouter C Meijers¹, Herman H W Silljé¹, Pieter Muntendam², Martin M Dokter¹, Wiek H van Gilst¹, Henk A Schols³, Rudolf A de Boer⁴

Affiliations

¹ Department of Cardiology, University of Groningen, University Medical Center Groningen, 9700 RB, Groningen, the Netherlands.
² scPharmaceuticals, Lexington, MA 02421-3105, MA, USA.
³ Wageningen University, Laboratory of Food Chemistry, 6708 WG, Wageningen, the Netherlands.
⁴ Department of Cardiology, University of Groningen, University Medical Center Groningen, 9700 RB, Groningen, the Netherlands. Electronic address: r.a.de.boer@umcg.nl.

PMID: 34826684
DOI: 10.1016/j.retram.2021.103321

Abstract

Purpose of the study: A major challenge in cardiology remains in finding a therapy for cardiac fibrosis. Inhibition of galectin-3 with pectins attenuates fibrosis in animal models of heart failure. The purpose of this study is to identify pectins with the strongest galectin-3 inhibitory capacity. We evaluated the in vitro inhibitory capacity, identified potent pectins, and tested if this potency could be validated in a mouse model of myocardial fibrosis.

Methods: Various pectin fractions were screened in vitro. Modified rhubarb pectin (EMRP) was identified as the most potent inhibitor of galectin-3 and compared to the well-known modified citrus pectin (MCP). Our findings were validated in a mouse model of myocardial fibrosis, which was induced by angiotensin II (Ang II) infusion.

Results: Ang II infusion was associated with a 4-5-fold increase in fibrosis signal in the tissue of the left ventricle, compared to the control group (0•22±0•10 to 1•08±0•53%; P < 0•001). After treatment with rhubarb pectin, fibrosis was reduced by 57% vs. Ang II alone while this reduction was 30% with the well-known MCP (P = NS, P < 0•05). Treatment was associated with a reduced cardiac inflammatory response and preserved cardiac function.

Conclusion: The galectin-3 inhibitor natural rhubarb pectin has a superior inhibitory capacity over established pectins, substantially attenuates cardiac fibrosis, and preserves cardiac function in vivo. Bioactive pectins are natural sources of galectin-3 inhibitors and may be helpful in the prevention of heart failure or other diseases characterized by fibrosis.

Funding: Dr. Meijers is supported by the Mandema-Stipendium of the Junior Scientific Masterclass 2020-10, University Medical Center Groningen and by the Netherlands Heart Foundation (Dekkerbeurs 2021)Dr. de Boer is supported by the Netherlands Heart Foundation (CVON SHE-PREDICTS-HF, grant 2017-21; CVON RED-CVD, grant 2017-11; CVON PREDICT2, grant 2018-30; and CVON DOUBLE DOSE, grant 2020B005), by a grant from the leDucq Foundation (Cure PhosphoLambaN induced Cardiomyopathy (Cure-PLaN), and by a grant from the European Research Council (ERC CoG 818715, SECRETE-HF).

Keywords: Affinity; Fibrosis; Galectin-3; Heart failure; Inhibitor; Pectin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Disease Models, Animal
Fibrosis
Galectin 3*
Mice
Pectins*

Substances

Galectin 3
Pectins