Resveratrol Improves Cardiac Function by Promoting M2-like Polarization of Macrophages in Mice with Myocardial Infarction

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2019 Sep 10

PMID 31497235

Citations 13

Authors

Shuiyuan Liu

Yingqiang Du

Kexin Shi

Yaqing Yang

Zhijian Yang

Affiliations

Soon will be listed here.

Abstract

Macrophage polarization determines the transition from the inflammation phase to the inflammation resolution phase after myocardial infarction (MI). The aim of the present study was to investigate whether resveratrol (RSV) could inhibit the inflammatory mediators associated with the regulation of macrophage phenotypes and functions in MI mice. We initially discovered that RSV significantly improved cardiac function and suppressed the expression of fibrosis markers, such as collagen-I, collagen-III, and fibronectin, and pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). RSV inhibited the expression of M1-like macrophage-related biomarkers (e.g., TNF-α and MCP-1) when bone marrow-derived macrophages (BMDMs) were stimulated with lipopolysaccharide (LPS) and interferon-γ (INF-γ). In contrast, it upregulated M2-like macrophage-related biomarkers (e.g., CD163 and Arg-1) when BMDMs were stimulated with interleukin-4 (IL-4) and interleukin-10 (IL-10). In addition, we found that RSV promoted M2-like macrophage polarization under anoxic conditions, which could be related to JAK2-SATA3 phosphorylation. In summary, RSV might promote anti-inflammatory M2-like polarization of macrophages after MI to improve cardiac function via the regulation of JAK2-SATA3 phosphorylation.

Citing Articles

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References

Kakio T, Matsumori A, Ono K, Ito H, Matsushima K, Sasayama S . Roles and relationship of macrophages and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in the ischemic and reperfused rat heart. Lab Invest. 2000; 80(7):1127-36. DOI: 10.1038/labinvest.3780119. View

Bradamante S, Barenghi L, Villa A . Cardiovascular protective effects of resveratrol. Cardiovasc Drug Rev. 2004; 22(3):169-88. DOI: 10.1111/j.1527-3466.2004.tb00139.x. View

Das S, Alagappan V, Bagchi D, Sharma H, Maulik N, Das D . Coordinated induction of iNOS-VEGF-KDR-eNOS after resveratrol consumption: a potential mechanism for resveratrol preconditioning of the heart. Vascul Pharmacol. 2005; 42(5-6):281-9. DOI: 10.1016/j.vph.2005.02.013. View

Gordon S, Taylor P . Monocyte and macrophage heterogeneity. Nat Rev Immunol. 2005; 5(12):953-64. DOI: 10.1038/nri1733. View

Fukuda S, Kaga S, Zhan L, Bagchi D, Das D, Bertelli A . Resveratrol ameliorates myocardial damage by inducing vascular endothelial growth factor-angiogenesis and tyrosine kinase receptor Flk-1. Cell Biochem Biophys. 2006; 44(1):43-9. DOI: 10.1385/CBB:44:1:043. View

Wang Z, Chen Y, Labinskyy N, Hsieh T, Ungvari Z, Wu J . Regulation of proliferation and gene expression in cultured human aortic smooth muscle cells by resveratrol and standardized grape extracts. Biochem Biophys Res Commun. 2006; 346(1):367-76. DOI: 10.1016/j.bbrc.2006.05.156. View

Chuah S, Moore P, Zhu Y . S-allylcysteine mediates cardioprotection in an acute myocardial infarction rat model via a hydrogen sulfide-mediated pathway. Am J Physiol Heart Circ Physiol. 2007; 293(5):H2693-701. DOI: 10.1152/ajpheart.00853.2007. View

Nahrendorf M, Swirski F, Aikawa E, Stangenberg L, Wurdinger T, Figueiredo J . The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med. 2007; 204(12):3037-47. PMC: 2118517. DOI: 10.1084/jem.20070885. View

Das S, Das D . Resveratrol: a therapeutic promise for cardiovascular diseases. Recent Pat Cardiovasc Drug Discov. 2008; 2(2):133-8. DOI: 10.2174/157489007780832560. View

10.

van den Borne S, Cleutjens J, Hanemaaijer R, Creemers E, Smits J, Daemen M . Increased matrix metalloproteinase-8 and -9 activity in patients with infarct rupture after myocardial infarction. Cardiovasc Pathol. 2008; 18(1):37-43. DOI: 10.1016/j.carpath.2007.12.012. View

11.

Hagemann T, Lawrence T, McNeish I, Charles K, Kulbe H, Thompson R . "Re-educating" tumor-associated macrophages by targeting NF-kappaB. J Exp Med. 2008; 205(6):1261-8. PMC: 2413024. DOI: 10.1084/jem.20080108. View

12.

Lambert J, Lopez E, Lindsey M . Macrophage roles following myocardial infarction. Int J Cardiol. 2008; 130(2):147-58. PMC: 2857604. DOI: 10.1016/j.ijcard.2008.04.059. View

13.

Brunner S, Winogradow J, Huber B, Zaruba M, Fischer R, David R . Erythropoietin administration after myocardial infarction in mice attenuates ischemic cardiomyopathy associated with enhanced homing of bone marrow-derived progenitor cells via the CXCR-4/SDF-1 axis. FASEB J. 2008; 23(2):351-61. DOI: 10.1096/fj.08-109462. View

14.

Martinez F, Helming L, Gordon S . Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol. 2008; 27:451-83. DOI: 10.1146/annurev.immunol.021908.132532. View

15.

Downey J, Cohen M . Why do we still not have cardioprotective drugs?. Circ J. 2009; 73(7):1171-7. DOI: 10.1253/circj.cj-09-0338. View

16.

Tabas I . Macrophage death and defective inflammation resolution in atherosclerosis. Nat Rev Immunol. 2009; 10(1):36-46. PMC: 2854623. DOI: 10.1038/nri2675. View

17.

Nahrendorf M, Pittet M, Swirski F . Monocytes: protagonists of infarct inflammation and repair after myocardial infarction. Circulation. 2010; 121(22):2437-45. PMC: 2892474. DOI: 10.1161/CIRCULATIONAHA.109.916346. View

18.

Schmidt T, Carmeliet P . Blood-vessel formation: Bridges that guide and unite. Nature. 2010; 465(7299):697-9. DOI: 10.1038/465697a. View

19.

Shen L, Gao Y, Qian J, Sun A, Ge J . A novel mechanism for endothelial progenitor cells homing: The SDF-1/CXCR4-Rac pathway may regulate endothelial progenitor cells homing through cellular polarization. Med Hypotheses. 2010; 76(2):256-8. DOI: 10.1016/j.mehy.2010.10.014. View

20.

Renga B . Hydrogen sulfide generation in mammals: the molecular biology of cystathionine-β- synthase (CBS) and cystathionine-γ-lyase (CSE). Inflamm Allergy Drug Targets. 2011; 10(2):85-91. DOI: 10.2174/187152811794776286. View