Resveratrol induces vascular smooth muscle cell differentiation through stimulation of SirT1 and AMPK.
Resveratrol induces vascular smooth muscle cell differentiation through stimulation of SirT1 and AMPK.
复制标题
DOI：
10.1371/journal.pone.0085495
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Rzucidlo EM
中科院分区：
文献类型：
--
作者：
Thompson AM;Martin KA;Rzucidlo EM
血管平滑肌细胞（VSMC）的表型可塑性是血管维持、修复和适应与衰老相关的血管变化所必需的。去分化的VSMC导致包括动脉粥样硬化和内膜增生的病理。由于白藜芦醇已被报道具有心脏保护作用，我们研究了其在VSMC表型调节中的作用。我们证明了新的发现，白藜芦醇促进血管平滑肌细胞分化的收缩蛋白表达，收缩形态和胶原凝胶收缩。白藜芦醇通过刺激SirT1和AMPK诱导VSMC分化。我们发现低剂量和高剂量白藜芦醇诱导分化的机制不同。我们发现，低剂量白藜芦醇通过SirT1介导的AKT活化来刺激分化，而高剂量白藜芦醇通过AMPK介导的mTORC 1通路抑制来刺激分化，从而激活AKT。白藜芦醇对心血管疾病、癌症和长寿的健康影响是一个活跃的研究领域。我们已经证明了一种补充途径，白藜芦醇可以通过维持和增强血管系统的可塑性来促进健康。
Phenotypic plasticity in vascular smooth muscle cells (VSMC) is necessary for vessel maintenance, repair and adaptation to vascular changes associated with aging. De-differentiated VSMC contribute to pathologies including atherosclerosis and intimal hyperplasia. As resveratrol has been reported to have cardio- protective effects, we investigated its role in VSMC phenotypic modulation. We demonstrated the novel finding that resveratrol promoted VSMC differentiation as measured by contractile protein expression, contractile morphology and contraction in collagen gels. Resveratrol induced VSMC differentiation through stimulation of SirT1 and AMPK. We made the novel finding that low or high dose resveratrol had an initially different mechanism on induction of differentiation. We found that low dose resveratrol stimulated differentiation through SirT1-mediated activation of AKT, whereas high dose resveratrol stimulated differentiation through AMPK-mediated inhibition of the mTORC1 pathway, allowing activation of AKT. The health effects of resveratrol in cardiovascular diseases, cancer and longevity are an area of active research. We have demonstrated a supplemental avenue where-by resveratrol may promote health by maintaining and enhancing plasticity of the vasculature.
登录
查看更多内容
Sirtuins是否可行的目标可以改善健康状态和寿命？
DOI：
10.1038/nrd3738
发表时间：
2012-06-01
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Baur JA;Ungvari Z;Minor RK;Le Couteur DG;de Cabo R
通讯作者：
de Cabo R
影响因子：
7.7
作者：
Fullerton MD;Steinberg GR
通讯作者：
Steinberg GR
影响因子：
4.8
作者：
Lan, Fan;Cacicedo, Jose M.;Ido, Yasuo
通讯作者：
Ido, Yasuo
DOI：
10.1146/annurev.pathol.4.110807.092250
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Haigis MC;Sinclair DA
通讯作者：
Sinclair DA
影响因子：
3.7
作者：
Ghosh HS;McBurney M;Robbins PD
通讯作者：
Robbins PD