Modified citrus pectin prevents isoproterenol-induced cardiac hypertrophy associated with p38 signalling and TLR4/JAK/STAT3 pathway

Biomed Pharmacother. 2021 Nov;143:112178. doi: 10.1016/j.biopha.2021.112178. Epub 2021 Sep 25.

Abstract

Modified citrus pectin (MCP) is a specific inhibitor of galectin-3 (Gal-3) that is regarded as a new biomarker of cardiac hypertrophy, but its effect is unclear. The aim of this study is to investigate the role and mechanism of MCP in isoproterenol (ISO)-induced cardiac hypertrophy. Rats were injected with ISO to induce cardiac hypertrophy and treated with MCP. Cardiac function was detected by ECG and echocardiography. Pathomorphological changes were evaluated by the haematoxylin eosin (H&E) and wheat germ agglutinin (WGA) staining. The hypertrophy-related genes for atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC), and the associated signal molecules were analysed by qRT-PCR and western blotting. The results show that MCP prevented cardiac hypertrophy and ameliorated cardiac dysfunction and structural disorder. MCP also decreased the levels of ANP, BNP, and β-MHC and inhibited the expression of Gal-3 and Toll-like receptor 4 (TLR4). Additionally, MCP blocked the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), but it promoted the phosphorylation of p38. Thus, MCP prevented ISO-induced cardiac hypertrophy by activating p38 signalling and inhibiting the Gal-3/TLR4/JAK2/STAT3 pathway.

Keywords: Cardiac hypertrophy; Galectin-3 (Gal-3); JAK2/STAT3 pathway; Modified citrus pectin (MCP); TLR4; p38 signalling.

MeSH terms

  • Animals
  • Atrial Natriuretic Factor / genetics
  • Atrial Natriuretic Factor / metabolism
  • Cardiomegaly / chemically induced
  • Cardiomegaly / drug therapy*
  • Cardiomegaly / enzymology
  • Cardiomegaly / physiopathology
  • Cardiovascular Agents / pharmacology*
  • Disease Models, Animal
  • Galectin 3 / metabolism
  • Isoproterenol
  • Janus Kinase 2 / metabolism*
  • Male
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / enzymology
  • Myocytes, Cardiac / pathology
  • Myosin Heavy Chains / genetics
  • Myosin Heavy Chains / metabolism
  • Natriuretic Peptide, Brain / genetics
  • Natriuretic Peptide, Brain / metabolism
  • Pectins / pharmacology*
  • Phosphorylation
  • Rats, Wistar
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • Toll-Like Receptor 4 / metabolism*
  • Ventricular Function, Left / drug effects
  • Ventricular Remodeling / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Cardiovascular Agents
  • Galectin 3
  • Lgals3 protein, rat
  • MYH7 protein, rat
  • STAT3 Transcription Factor
  • Stat3 protein, rat
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Natriuretic Peptide, Brain
  • citrus pectin
  • Atrial Natriuretic Factor
  • Pectins
  • Jak2 protein, rat
  • Janus Kinase 2
  • p38 Mitogen-Activated Protein Kinases
  • Myosin Heavy Chains
  • Isoproterenol