Curcumin Ameliorates Cardiac Fibrosis by Regulating Macrophage-Fibroblast Crosstalk via IL18-P-SMAD2/3 Signaling Pathway Inhibition

30Citations
Citations of this article
31Readers
Mendeley users who have this article in their library.
Get full text

Abstract

Ethnopharmacological relevance: Curcumin is a bright yellow chemical produced by plants of the Curcuma longa species. Chemically, curcumin is a diarylheptanoid, belonging to the group of curcuminoids. The therapeutic potential of curcumin has been widely investigated, including its utilization in various of cardiovascular diseases. However, its effect in cardiac remodeling post myocardial infarction and underlying mechanism remains to be uncover. Aim: To evaluate the therapeutic effect and underlying mechanism of curcumin on cardiac fibrosis after myocardial infarction via macrophage-fibroblast crosstalk. Methods: Male C57BL/6 (C57) mice were subjected to left anterior descending coronary artery ligation to establish myocardial infarction and intragastrically fed vehicle or curcumin (50 mg/kg or 100 mg/kg) for 4 weeks. In parallel, neonatal rat cardiac fibroblasts were isolated and co-cultured with liposaccharide (LPS− or LPS+) curcumin-treated macrophages, followed by TGF-β stimulation for 24 h. Cardiac function was determined by 2-dimensional echocardiography, and cardiac fibrosis was measured by picrosirius red staining. Apoptosis of macrophages was investigated by flow cytometry; all pro-fibrotic protein expression (EDA-Fibronectin, Periostin, Vimentin, and α-SMA) as well as TGF-βR1 downstream signaling activation reflected by phosphorylated SMAD2/3 (p-SMAD2 and p-SMAD3) were demonstrated by western blotting. Results: Curcumin significantly ameliorated the inflammation process subsequent to myocardial infarction, reflected by decreased expression of CD68+ and CD3+ cells, accompanied by dramatically improved cardiac function compared with the placebo group. In addition, cardiac fibrosis is inhibited by curcumin administration. Interestingly, no significant reduction in fibrotic gene expression was observed when isolated cardiac fibroblasts were directly treated with curcumin in vitro; however, pro-fibrotic protein expression was significantly attenuated in CF, which was co-cultured with LPS-stimulated macrophages under curcumin treatment compared with the placebo group. Mechanistically, we discovered that curcumin significantly downregulated pro-inflammatory cytokines in macrophages, which in turn inhibited IL18 expression in co-cultured cardiac fibroblasts using bulk RNA sequencing, and the TGF-β1-p-SMAD2/3 signaling network was also discovered as the eventual target downstream of IL18 in curcumin-mediated anti-fibrosis signaling. Conclusion: Curcumin improves cardiac function and reduces cardiac fibrosis after myocardial infarction. This effect is mediated by the inhibition of macrophage-fibroblast crosstalk in the acute phase post-MI and retrained activation of IL18-TGFβ1-p-SMAD2/3 signaling in cardiac fibroblasts.

References Powered by Scopus

Macrophages in Tissue Repair, Regeneration, and Fibrosis

2918Citations
N/AReaders
Get full text

The pathogenesis of cardiac fibrosis

1276Citations
N/AReaders
Get full text

Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation

1135Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Transforming growth factor-β signaling: From tissue fibrosis to therapeutic opportunities

76Citations
N/AReaders
Get full text

Injectable decellularized extracellular matrix hydrogel loaded with exosomes encapsulating curcumin for prevention of cardiac fibrosis after myocardial infarction

28Citations
N/AReaders
Get full text

The role of adiponectin in cardiovascular disease

28Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Zhao, J., Chen, Y., Chen, Q., Hong, T., Zhong, Z., He, J., & Ni, C. (2022). Curcumin Ameliorates Cardiac Fibrosis by Regulating Macrophage-Fibroblast Crosstalk via IL18-P-SMAD2/3 Signaling Pathway Inhibition. Frontiers in Pharmacology, 12. https://doi.org/10.3389/fphar.2021.784041

Readers over time

‘22‘23‘24‘25036912

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 5

71%

Professor / Associate Prof. 1

14%

Researcher 1

14%

Readers' Discipline

Tooltip

Medicine and Dentistry 2

33%

Biochemistry, Genetics and Molecular Bi... 2

33%

Design 1

17%

Agricultural and Biological Sciences 1

17%

Save time finding and organizing research with Mendeley

Sign up for free
0