Intense Light-Mediated Circadian Cardioprotection via Transcriptional Reprogramming of the Endothelium

被引：34
作者：
Oyama, Yoshimasa [1 ,2 ]
Bartman, Colleen M. [1 ,2 ,5 ]
Bonney, Stephanie [1 ,2 ,5 ]
Lee, J. Scott [1 ,2 ]
Walker, Lori A. [3 ]
Han, Jun [4 ]
Borchers, Christoph H. [4 ,6 ,7 ]
Buttrick, Peter M. [3 ]
Aherne, Carol M. [1 ,2 ]
Clendenen, Nathan [1 ,2 ]
Colgan, Sean P. [1 ,2 ]
Eckle, Tobias [1 ,2 ,3 ,5 ]
机构：
[1] Univ Colorado, Dept Med, Mucosal Inflammat Program, Anschutz Med Campus, Aurora, CO 80045 USA
[2] Univ Colorado, Dept Anesthesiol, Mucosal Inflammat Program, Anschutz Med Campus, Aurora, CO 80045 USA
[3] Univ Colorado, Dept Med, Div Cardiol, Anschutz Med Campus, Aurora, CO USA
[4] Univ Victoria, Genome BC Prote Ctr, Dept Biochem & Microbiol, Victoria, BC, Canada
[5] Univ Colorado, Grad Training Programin Cell Biol Stem Cells & De, AnschutzMedical Campus, Aurora, CO USA
[6] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Segal Canc Prote Ctr, Montreal, PQ, Canada
[7] McGill Univ, Jewish Gen Hosp, Gerald Bronfman Dept Oncol, Montreal, PQ, Canada
来源：
CELL REPORTS | 2019年 / 28卷 / 06期
关键词：
HYPOXIA-INDUCIBLE FACTOR-1; PENTOSE-PHOSPHATE PATHWAY; MYOCARDIAL-INFARCTION; GENE-EXPRESSION; CENTRAL CARBON; BRIGHT LIGHT; CLOCK GENE; PER2; METABOLISM; COMPONENT;
D O I：
10.1016/j.celrep.2019.07.020
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Consistent daylight oscillations and abundant oxygen availability are fundamental to human health. Here, we investigate the intersection between light-sensing (Period2 [PER2]) andoxygen-sensing (hypoxia-inducible factor [HIF1A]) pathways in cellular adaptation to myocardial ischemia. We demonstrate that intense light is cardioprotective via circadian PER2 amplitude enhancement, mimicking hypoxia-elicited adeno-sine- and HIF1A-metabolic adaptation to myocardial ischemia under normoxic conditions. Whole-genome array fromintense light-exposed wild-type or Per2(-/-) mice and myocardial ischemia in endothelial-specific PER2-deficient mice uncover a critical role for intense light in maintaining endothelial barrier function via light-enhanced HIF1A transcription. A proteomics screen in human endothelia reveals a dominant role for PER2 in metabolic reprogramming to hypoxia via mitochondrial translocation, tricarboxylic acid (TCA) cycle enzyme activity regulation, and HIF1A transcriptional adaption to hypoxia. Translational investigation of intense light in human subjects identifies similar PER2 mechanisms, implicating the use of intense light for the treatment of cardiovascular disease.
引用
收藏
页码：1471 / +
页数：25
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