Divergent Effects of Resveratrol on Rat Cardiac Fibroblasts and Cardiomyocytes

Abstract

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.

Polyphenols’ Cardioprotective Potential: Review of Rat Fibroblasts as Well as Rat and Human Cardiomyocyte Cell Lines Research

“…The effect of different polyphenols on fibroblast cardiomyocytes, AC16 [ 17 ], myofibroblasts [ 23 ], H9c2 [ 10 , 11 , 13 , 18 , 19 , 24 , 25 , 27 , 28 ], neonatal rat cardiomyocytes [ 10 , 11 ], primary rat adult fibroblasts [ 23 ], rat cardiomyocytes [ 12 , 15 , 20 , 21 , 22 , 23 , 26 , 30 , 31 ], as well as young and old human cardiomyocytes [ 29 ] was analyzed by different groups.…”

“…The increase in apoptotic cells with condensed nuclei by 72 and 62% was observed in resveratrol treated fibroblasts and myofibroblasts, respectively. In contrast, resveratrol did not cause apoptosis in cardiomyocytes [ 23 ].…”

“…The effect of resveratrol on primary rat adult fibroblasts, myofibroblasts, and cardiomyocytes was analyzed by Louis et al (2019). The authors showed that resveratrol (30 and 60 µM) significantly reduced the viability of fibroblasts and myofibroblasts, while it did not alter cardiomyocyte viability.…”

“…Polyphenols have gained interest due to their cardioprotective effect, which is related to antioxidative activity [ 10 , 11 , 12 , 13 , 14 , 15 ], anti-inflammatory activity [ 11 , 16 , 17 , 18 ], modulation and synchronization of cardiomyocyte beating [ 10 ], and protection against cell apoptosis [ 11 , 13 , 14 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ], cardiac hypertrophy [ 11 , 21 , 25 , 26 ], and atherosclerosis ischemia/reperfusion injuries [ 4 , 11 , 12 , 13 , 15 , 18 ].…”

“…Polyphenols have gained interest due to their cardioprotective effect, which is related to antioxidative activity [10][11][12][13][14][15], anti-inflammatory activity [11,[16][17][18], modulation and synchronization of cardiomyocyte beating [10], and protection against cell apopto- Polyphenols have gained interest due to their cardioprotective effect, which is related to antioxidative activity [10][11][12][13][14][15], anti-inflammatory activity [11,[16][17][18], modulation and synchronization of cardiomyocyte beating [10], and protection against cell apoptosis [11,13,14,[19][20][21][22][23][24][25], cardiac hypertrophy [11,21,25,26], and atherosclerosis ischemia/reperfusion injuries [4,[11][12][13]15,18].…”