Yamaura Takeshi, Kasaoka Tatsuhiko, Iijima Naoko, Kimura Masaaki, Hatakeyama Shinji
Novartis Institutes for BioMedical Research, Novartis Pharma K.K, Tsukuba, Ibaraki, Japan.
Novartis Pharma AG, Basel, Switzerland.
BMC Res Notes. 2019 Apr 2;12(1):200. doi: 10.1186/s13104-019-4220-5.
Therapeutic effects of focal adhesion kinase (FAK) inhibition using a small molecule inhibitor was evaluated in apolipoprotein E (apoE) knockout (KO) and low-density lipoprotein receptor (LDLr) KO mouse atherosclerosis models.
The prevention trial consisted of an 8-week treatment with an FAK inhibitor concurrent treatment with a high fat (HF)/high cholesterol (HC) diet. The intervention trial consisted of 6- and 8-week treatment after 6- and 8-week pre-loading, respectively, of a HF/HC diet in apoE KO and LDLr KO mice, respectively. The inhibitor was admixed with a HF/HC diet and mice were given free access to the admixture. The FAK inhibitor exhibited marked inhibition against the development of the atherosclerosis in both of prevention and intervention trials at a dose of 0.03% without showing any remarkable toxic properties in biochemical examinations. These results indicated that FAK inhibition might be a possible candidate for novel therapeutic targets against atherosclerosis.
在载脂蛋白E（apoE）基因敲除（KO）和低密度脂蛋白受体（LDLr）基因敲除小鼠动脉粥样硬化模型中评估使用小分子抑制剂抑制粘着斑激酶（FAK）的治疗效果。
预防试验包括用FAK抑制剂进行为期8周的治疗，并同时给予高脂（HF）/高胆固醇（HC）饮食。干预试验分别在apoE基因敲除和LDLr基因敲除小鼠中，在分别给予6周和8周的HF/HC饮食预负荷后，进行6周和8周的治疗。将抑制剂与HF/HC饮食混合，让小鼠自由摄取该混合物。在预防和干预试验中，FAK抑制剂以0.03%的剂量对动脉粥样硬化的发展均表现出显著抑制作用，且在生化检查中未显示出任何明显的毒性。这些结果表明，抑制FAK可能是抗动脉粥样硬化新治疗靶点的一个潜在候选。
