Preventive and treatment efficiency of dendrosomal nano-curcumin against ISO-induced cardiac fibrosis in mouse model

PLoS One. 2024 Oct 10;19(10):e0311817. doi: 10.1371/journal.pone.0311817. eCollection 2024.

Abstract

Cardiac fibrosis (c-fibrosis) is a critical factor in cardiovascular diseases, leading to impaired cardiac function and heart failure. This study aims to optimize the isoproterenol (ISO)-induced c-fibrosis model and evaluate the therapeutic efficacy of dendrosomal nano-curcumin (DNC) in both in-vitro and in-vivo conditions. Also, we were looking for the differentially expressed genes following the c-fibrosis induction. At the in-vitro condition, primary cardiac fibroblasts were exclusively cultured on collagen-coated or polystyrene plates and, were treated with ISO for fibrosis induction and post-treated or co-treated with DNC. RT-qPCR and flow cytometry analysis indicated that DNC treatment attenuated the fibrotic effect of ISO treatment in these cells. At the in-vivo condition, our findings demonstrated that ISO treatment effectively induces cardiac (and pulmonary) fibrosis, characterized by pro-fibrotic and pro-inflammatory gene expression and IHC (α-SMA, COL1A1, and TGFβ). Interestingly, fibrosis symptoms were reduced following the pretreatment, co-treatment, or post-treatment of DNC with ISO. Additionally, the intensive RNAseq analysis suggested the COMP gene is differentially expressed following the c-fibrosis and our RT-qPCR analysis suggested it as a novel potential marker. Overall, our results promise the application of DNC as a potential preventive or therapy agent before and after heart challenges that lead to c-fibrosis.

MeSH terms

  • Animals
  • Curcumin* / pharmacology
  • Dendrimers / chemistry
  • Dendrimers / pharmacology
  • Disease Models, Animal*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibrosis*
  • Isoproterenol*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocardium* / metabolism
  • Myocardium* / pathology
  • Nanoparticles / chemistry

Substances

  • Curcumin
  • Isoproterenol
  • Dendrimers

Grants and funding

This work is based upon research funded by Tarbiat Modares University and Iran National Science Foundation (INSF) under project No.4014277. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.