FOXO proteins and protection from cardiac ischaemic injury

心脏供血减少会引发心脏病发作，导致心肌受损。在这种情况下，肌肉组织的丧失会引发心脏的病理性生长，最终可能导致心力衰竭，心力衰竭是西方国家死亡和残疾的主要原因。用生长因子治疗可以防止细胞的急性损伤和丢失，但这会对其他组织造成不利影响。出于这些原因，有必要建立一种方法来激活心脏中的保护通路，而不会对其他组织造成不必要的影响。为此，我们首次在心脏中发现了一个新描述的基因调节家族成员，该家族可以通过增加细胞毒因子的表达而导致细胞死亡。我们证明了这些FKHR或FOXO家族成员在心脏中受到调节，并活跃地产生细胞毒因子。我们现在计划确定FOXO蛋白是否参与了心脏病发作期间导致细胞死亡的过程，以及操纵它们的活动是否可以保护心脏。

Reduced blood supply to the heart can initiate a heart attack that results in damage to the heart muscle. Loss of muscle tissue under these conditions initiates pathological growth of the heart and can eventually lead to the development of heart failure, a major cause of death and disability in western countries. Treatment with growth factors can prevent the acute damage and loss of cells, but these cause detrimental effects on other tissues. For these reasons, it is necessary to establish ways to activate protective pathways in the heart without causing unwanted effects on other tissues. To this end, we have identified for the first time in the heart members of a newly described family of gene regulators that can cause cell death by increasing expression of cytotoxic factors. We showed that these FKHRor FOXO family members are regulated in the heart and that they are active in generating cytotoxic factors. We now plan to establish whether FOXO proteins are involved in causing cell death during heart attack and whether manipulating their activities can be cardioprotective.