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

Purpose of the study: A major challenge in cardiology remains in finding a therapy for cardiac fibrosis. Inhibi-tion 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 myocar-dial 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 ven-tricle, 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).(c) 2021 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Automated summary

The study aimed to find a therapy for cardiac fibrosis and identified rhubarb pectin as a potent inhibitor of galectin-3. The effectiveness of rhubarb pectin was validated in a mouse model of myocardial fibrosis, showing significant reduction of fibrosis and preserved cardiac function.