FOXO proteins and protection from cardiac ischaemic injury

FOXO 蛋白与心脏缺血性损伤的保护

• 批准号: nhmrc : 317801
• 负责人: A/Pr Elizabeth Woodcock
• 金额: $ 23.63万
• 依托单位: Baker IDI Heart and Diabetes Institute
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/foxo-proteins-protection-ischaemic-injury/100184
• 关键词: FOXO; proteins; protection; cardiac; ischaemic

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.

心脏供血减少会引发心脏病发作，导致心肌损伤。在这些条件下肌肉组织的损失引发心脏的病理性生长，并最终导致心力衰竭的发展，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损失，但这些会对其他组织产生有害影响。由于这些原因，有必要建立激活心脏保护通路的方法，而不会对其他组织造成不必要的影响。为此，我们首次在心脏中鉴定了一个新描述的基因调节子家族的成员，该家族可以通过增加细胞毒性因子的表达引起细胞死亡。我们发现这些FKHR或FOXO家族成员在心脏中受到调节，并且它们在产生细胞毒性因子中是活跃的。我们现在计划确定FOXO蛋白是否参与心脏病发作期间引起细胞死亡，以及操纵它们的活动是否可以保护心脏。