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首页> 外文期刊>Cell cycle >Hypercholesterolemia is associated with hyperactive cardiac mTORC1 and mTORC2 signaling.
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Hypercholesterolemia is associated with hyperactive cardiac mTORC1 and mTORC2 signaling.

机译：高胆固醇血症与心脏过度活跃的mTORC1和mTORC2信号传导有关。

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Nutritional excess and hyperlipidemia increase the heart's susceptibility to ischemic injury. Mammalian target of rapamycin (mTOR) controls the cellular response to nutritional status and may play a role in ischemic injury. To explore the effect of hypercholesterolemia on cardiac mTOR signaling, we assessed mTOR signaling in hypercholesterolemic swine (HC) that are also susceptible to increased cardiac ischemia-reperfusion injury. Yucatan pigs were fed a high-fat/high-cholesterol diet for 4 weeks to induce hypercholesterolemia, and mTOR signaling was measured by immunoblotting and immunofluorescence in the non-ischemic left ventricular area. Total myocardial mTOR and raptor levels were markedly increased in the HC group compared to the normocholesterolemic group, and directly correlated with serum cholesterol levels. mTOR exhibited intense perinuclear staining in myocytes only in the HC group. Hypercholesterolemia was associated with hyperactive signaling upstream and downstream of both mTOR complexes, including myocardial Akt, S6K1, 4EBP1, S6 and PKC-alpha, increased levels of cardiac hypertrophy markers, and a trend toward lower levels of myocardial autophagy. Hypercholesterolemia can now be added to the growing list of conditions associated with aberrant mTOR signaling. Hypercholesterolemia produces a unique profile of alterations in cardiac mTOR signaling, which is a potential target in cardiac diseases associated with hypercholesterolemia and nutritional excess.
机译：营养过剩和高脂血症会增加心脏对缺血性损伤的敏感性。雷帕霉素的哺乳动物靶标（mTOR）控制细胞对营养状况的反应，并可能在缺血性损伤中起作用。为了探索高胆固醇血症对心脏mTOR信号的影响，我们评估了高胆固醇血症猪（HC）中的mTOR信号，该猪也容易增加心脏缺血-再灌注损伤。尤卡坦猪饲喂高脂/高胆固醇饮食4周以诱导高胆固醇血症，并通过免疫印迹和免疫荧光在非缺血性左心室区域测量mTOR信号传导。与正常胆固醇血症组相比，HC组的总心肌mTOR和猛禽水平显着增加，并且与血清胆固醇水平直接相关。仅在HC组中，mTOR在肌细胞中显示出强烈的核周染色。高胆固醇血症与包括心肌Akt，S6K1、4EBP1，S6和PKC-α在内的两种mTOR复合体的上游和下游信号活跃有关，心肌肥大标志物水平升高，心肌自噬水平降低。高胆固醇血症现在可以添加到与异常mTOR信号传导相关的越来越多的病症中。高胆固醇血症会产生独特的心脏mTOR信号变化，这是与高胆固醇血症和营养过剩相关的心脏病的潜在靶标。

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