Statins induce the glucocorticoid-induced leucine zipper protein GILZ: mechanisms and functional implications

他汀类药物是世界上使用最广泛的一类药物。它们对心血管疾病具有独特的保护作用，这是通过降脂和抗炎作用促进的。肌病是最常见的副作用，其范围从轻度肌肉疼痛到危及生命的横纹肌溶解。据报道，糖皮质激素诱导的亮氨酸拉链蛋白GILZ具有明显的抗炎作用。该项目的目的是验证这样一种假设，即GILZ的诱导实质上有助于他汀类药物的预期作用，但GILZ也在其不良影响中发挥作用。为了验证这一假设，以下问题将得到回答：-他汀类药物在哪些细胞类型中诱导GILZ？-诱导GILZ的机制是什么？- GILZ是否有助于他汀类药物的抗炎作用？- GILZ诱导是否促进他汀类药物对肌肉的作用？回答这些问题可以大大有助于更好地了解这类重要药物的作用机制，但也可以帮助更好地了解不良副作用。

Statins represent the most widely prescribed class of drugs worldwide. They convey a distinct protection from cardiovascular pathologies, which are facilitated via both lipid-lowering and anti-inflammatory actions. Myopathies represent the most common side effects, which range from mild muscle pain to life-threatening rhabdomyolyses. The glucocortioid induced leucine zipper protein GILZ has been reported to exhibit distinct anti-infammatory actions. Aim of the project is to test the hypothesis that the induction of GILZ substantially contributes to the desired actions of statins, but that GILZ also plays a role in their undesired effects. The following questions will be answered in order to test the hypothesis:- In which cell types do statins induce GILZ?- What are the mechanisms for GILZ induction?- Does GILZ contribute to the anti-inflammatory actions of statins?- Does GILZ induction facilitate effects of statins on muscle?Answering these questions can substantially contribute to a better understanding of the mechanisms of action of this important class of drugs, but can also help to better understand adverse side effects.