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. 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).

Galectin-3 and heart failure: prognosis, prediction & clinical utility.

Heart failure (HF) is a leading cause of mortality in the western world. Despite advances in the treatment of HF, like the use of angiotensin-converting enzyme (ACE) inhibitors, ß-blockers, angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs), and implantable cardiac defibrillators, prognosis of HF patients remains poor. For clinicians dealing with HF patients, risk prediction in both acute, chronic, and new onset HF remains a challenge. Biomarkers might help in risk stratification and may guide the proper use of limited resources and therapy. Galectin-3 is an emerging biomarker which has been linked to tissue fibrosis, a hallmark in cardiac remodeling and HF. Galectin-3 can reliably be measured in the circulation, and several recent studies have shown the prognostic value of galectin-3 in acute and chronic HF, and its potential utility in the general population. The purpose of this review was to summarize the literature and explore the potential role of galectin-3 as a biomarker in HF.