Evaluation of therapeutic effects of FAK inhibition in murine models of atherosclerosis.

Authors:
Takeshi Yamaura
Takeshi Yamaura
Pharmaceutical and Healthcare Research Laboratories
Tatsuhiko Kasaoka
Tatsuhiko Kasaoka
Tsukuba Research Institute
Japan
Masaaki Kimura
Masaaki Kimura
Tsukuba Research Institute
Japan
Shinji Hatakeyama
Shinji Hatakeyama
Novartis Institutes for Biomedical Research
Switzerland

BMC Res Notes 2019 Apr 2;12(1):200. Epub 2019 Apr 2.

Novartis Pharma AG, Basel, Switzerland.

Objective: 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.

Results: 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.

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https://bmcresnotes.biomedcentral.com/articles/10.1186/s1310
Publisher Site
http://dx.doi.org/10.1186/s13104-019-4220-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446301PMC
April 2019
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