title: Chronic circadian clock disruption induces expression of the cardiovascular risk factor plasminogen activator inhibitor-1 in mice.
abstract: Links between shift work and increases in metabolic risk factors for cardiovascular diseases have been documented in detail, although the underlying causes remain obscure. Plasminogen activator inhibitor-1 (PAI-1) is a key regulator of fibrinolysis that is also associated with an increased risk of cardiovascular diseases. We examined the effect of experimental chronic circadian clock disruption on PAI-1 expression in mice. Mice were exposed to chronic phase shifts and fed with a high-fat/high-sucrose diet. Chronic phase shifts resulted in increased plasma PAI-1 level through inducing PAI-1 mRNA expression and decreasing tissue-type plasminogen activator (tPA) mRNA expression in the liver. Chronic circadian clock disruption might induce hypofibrinolysis and increase the risk of cardiovascular events by inducing the PAI-1 gene expression in obese individuals.
authors.affiliation: Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan.
authors.forename: Katsutaka
authors.initials: K
authors.lastname: Oishi
authors.forename: Naoki
authors.initials: N
authors.lastname: Ohkura
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology*; D002908:Chronic Disease; D021081:Chronobiology Disorders / Q000097:blood* / Q000150:complications / Q000235:genetics; D003345:Corticosterone / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D019422:Dietary Sucrose / Q000633:toxicity; D005342:Fibrinolysis; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009765:Obesity / Q000150:complications; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D058258:Serpin E2 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D019851:Thrombophilia / Q000209:etiology / Q000503:physiopathology; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics
chemical_list: D019422:Dietary Sucrose; D012333:RNA, Messenger; D058258:Serpin E2; C511869:Serpine2 protein, mouse; D010959:Tissue Plasminogen Activator; D003345:Corticosterone