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Resveratrol attenuates apoptosis of pulmonary microvascular endothelial cells induced by high shear stress and proinflammatory factors

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Abstract

Endothelial injury usually underlies the initial pathologic step of cardiovascular diseases. Primary endothelial cell (EC) apoptosis and secondary hyperproliferation both contribute to the development of atherosclerosis and luminal occlusion. In order to investigate the effects of resveratrol (RSV) on EC apoptosis, we applied high shear stress (HSS) with proinflammatory factors [tumor necrosis factor alpha (TNF-α) plus cycloheximide] to human pulmonary microvascular ECs (PMVECs) through an artificial capillary system. Intracellular reactive oxygen species (ROS) was measured by spectrofluorometry using dihydrorhodamine 123 fluorescent probe. Apoptosis and proliferation was determined by flow cytometric analysis. Protein expression was examined by Western blot. HSS plus inflammation significantly raised the ROS and the apoptosis level of PMVECs, which could be diminished by RSV pretreatment. In a 7-days incubation assay, RSV effectively inhibited the initial increase in apoptosis and thereby prevented subsequent PMVEC hyperproliferation induced by HSS plus inflammation. Mercaptosuccinate, a glutathione peroxidase (GPx-1) inhibitor or nicotinamide, a silent information regulator 2/sirtuin 1 (SIRT1) inhibitor could attenuate the antiapoptotic action of RSV on PMVECs; and RSV treatment upregulated GPx-1 and SIRT1 expression in PMVECs. In conclusion, RSV, probably by activating SIRT1 signaling pathway, inhibits the oxidative-stress-dependent phenotypical shift of ECs induced by HSS and proinflammatory factors in vitro.

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Acknowledgments

This study was financially supported by National Natural Science Foundation of China (No. 81001435).

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Authors and Affiliations

  1. Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, No. 3 Qingchun East Road, Hangzhou, 310016, Zhejiang, People’s Republic of China

    Liang Xia, Fang Ding, Jun-Hui Zhu & Guo-Sheng Fu

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  1. Liang Xia
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  2. Fang Ding
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  3. Jun-Hui Zhu
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  4. Guo-Sheng Fu
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Correspondence to Guo-Sheng Fu.

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Xia, L., Ding, F., Zhu, JH. et al. Resveratrol attenuates apoptosis of pulmonary microvascular endothelial cells induced by high shear stress and proinflammatory factors. Human Cell 24, 127–133 (2011). https://doi.org/10.1007/s13577-011-0031-2

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  • DOI: https://doi.org/10.1007/s13577-011-0031-2

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