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Open AccessArticle

Divergent Effects of Resveratrol on Rat Cardiac Fibroblasts and Cardiomyocytes

1
Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada
2
Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB R3E 0J9, Canada
3
Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada
4
Agriculture and Agri-Food Canada, Winnipeg Winnipeg, MB R2H 2A6, Canada
5
Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada
*
Authors to whom correspondence should be addressed.
Academic Editor: Philippe Jeandet
Molecules 2019, 24(14), 2604; https://doi.org/10.3390/molecules24142604
Received: 11 April 2019 / Revised: 11 July 2019 / Accepted: 12 July 2019 / Published: 17 July 2019
(This article belongs to the Special Issue Resveratrol: From the Farm to the Clinic)
In this study, we tested the potential cardioprotective effects of the phytoalexin resveratrol (Rsv) on primary adult rat cardiac fibroblasts (CF), myofibroblasts (MF) and cardiomyocytes. Adult rat CF and cardiomyocytes were isolated from male 10-week old Sprague–Dawley rats, cultured for either 24 h (cardiomyocytes) or 48 h (CF) before treatments. To isolate MF, CF were trypsinized after 48 h in culture, seeded in fresh plates and cultured for 24 h prior to treatment. All three cells were then treated for a further 24 h with a range of Rsv doses. In CF and MF, cell proliferation, viability, apoptosis assays were performed with or without Rsv treatment for 24 h. In cardiomyocytes, cell viability and apoptosis assay were performed 24 h after treatment. In separate experiments, CF was pre-incubated with estrogen, tamoxifen and fulvestrant for 30 min prior to Rsv treatment. Rsv treatment decreased proliferation of both fibroblasts and myofibroblasts. Rsv treatment also increased the proportion of dead CF and MF in a dose dependent manner. However, treatment with Rsv did not induce cell death in adult cardiomyocytes. There was an increase in the percentage of cells with condensed nuclei with Rsv treatment in both CF and MF, but not in cardiomyocytes. Treatment with estrogen, tamoxifen and fulvestrant alone or in combination with Rsv did not have any additional effects on CF survival. Our results demonstrate that treatment with Rsv can inhibit cell proliferation and induce cell death in rat CF and MF, while not affecting cardiomyocyte survival. We also demonstrated that the induction of cell death in CF with Rsv treatment was independent of estrogen receptor alpha (ERα) signaling. View Full-Text
Keywords: cardiac fibrosis; resveratrol; cardiac fibroblasts; cardiomyocytes cardiac fibrosis; resveratrol; cardiac fibroblasts; cardiomyocytes
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MDPI and ACS Style

Lieben Louis, X.; Meikle, Z.; Chan, L.; DeGagne, G.; Cummer, R.; Meikle, S.; Krishnan, S.; Yu, L.; Netticadan, T.; Wigle, J.T. Divergent Effects of Resveratrol on Rat Cardiac Fibroblasts and Cardiomyocytes. Molecules 2019, 24, 2604.

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