pectins and Cardiomyopathies

Topics: Cardiomyopathies; Glucosephosphate Dehydrogenase Deficiency; Glucosidases; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Hepatomegaly; Humans; Kidney Diseases; Liver Cirrhosis; Liver Diseases; Liver Glycogen; Muscular Diseases; Pectins; Polysaccharides; Splenomegaly

Myocardial fibrosis (MF) plays a key role in the development and progression of heart failure (HF) with limited effective therapies. Galectin-3 (Gal-3) is a biomarker associated with fibrosis and inflammation in patients with HF. The Gal-3 inhibitor modified citrus pectin (MCP) protects against cardiac dysfunction, though the underlying mechanism remains unclear. The aim of this study was to investigate the effect and mechanism of MCP on MF using an isoproterenol (ISO)-induced rat model of HF. Cardiac function was analyzed by echocardiography and electrocardiography. Histopathological changes in the heart tissue were assessed by hematoxylin-eosin and Masson trichrome staining. The mRNA and protein expression levels of signaling molecules and pro-inflammatory cytokines were monitored by immunohistochemistry, western blot, qRT-PCR and ELISA analyses. The results demonstrated that MCP ameliorated cardiac dysfunction, decreased myocardial injury and reduced collagen deposition. Furthermore, MCP downregulated the expression of Gal-3, TLR4 and MyD88, thereby inhibiting NF-κB-p65 activation. MCP also decreased the expression of IL-1β, IL-18 and TNF-α, which have been implicated in the pathogenesis of HF. These inhibitory effects were observed on day 15 and continued until day 22. Taken together, these results suggest that MCP ameliorates cardiac dysfunction through inhibiting inflammation and MF. These effects may be through downregulating Gal-3 expression and suppressing activation of the TLR4/MyD88/NF-κB signaling pathway. The present study supports the use of Gal-3 as a therapeutic target for the treatment of MF after myocardial infarction.

Topics: Animals; Biomarkers; Biopsy; Cardiomyopathies; Cytokines; Disease Susceptibility; Echocardiography; Electrocardiography; Fibrosis; Galectin 3; Heart Function Tests; Immunohistochemistry; Inflammation; Inflammation Mediators; Male; Models, Biological; Myeloid Differentiation Factor 88; NF-kappa B; Pectins; Rats; Signal Transduction; Toll-Like Receptor 4

Preclinical studies have demonstrated that anti-galectin-3 (Gal-3) interventions are effective in attenuating cardiac remodeling, fibrosis, and dysfunction. We determined, in a transgenic (TG) mouse model of fibrotic cardiomyopathy, whether Gal-3 expression was elevated and whether Gal-3 played a critical role in disease development. We studied mice with fibrotic cardiomyopathy attributable to cardiac overexpression of human β

Topics: Amino Sugars; Animals; Cardiomyopathies; Disease Models, Animal; Fibrosis; Galectin 3; Genetic Predisposition to Disease; Humans; Male; Mice, Inbred C57BL; Mice, Knockout; Myocytes, Cardiac; Pectins; Phenotype; Receptors, Adrenergic, beta-2; Severity of Illness Index; Up-Regulation; Ventricular Remodeling