Intense light as anticoagulant therapy in humans

• Published in: PloS one Vol. 15; no. 12; p. e0244792
• Main Authors: Oyama, Yoshimasa, Shuff, Sydney, Davizon-Castillo, Pavel, Clendenen, Nathan, Eckle, Tobias
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31-12-2020; Public Library of Science (PLoS)
• Subjects: Anesthesiology; Animal tissues; Animals; Anticoagulants; Anticoagulants (Medicine); Biology and Life Sciences; Blood coagulation; Blood Coagulation - physiology; Blood plasma; Blood platelets; Blood Platelets - metabolism; Calcium-binding protein; Circadian rhythm; Circadian rhythms; Clotting; Coagulation; Evaluation; Human performance; Human tissues; Humans; Injuries; Ischemia; Laboratory animals; Light; Light therapy; Male; Mammals; Medicine and Health Sciences; Mice; Myocardial ischemia; Myocardial Ischemia - blood; Myocardial Ischemia - metabolism; Myocardial Reperfusion Injury - blood; Myocardial Reperfusion Injury - metabolism; Period 2 protein; Period Circadian Proteins - genetics; Period Circadian Proteins - metabolism; Phototherapy; Plasma; Platelet aggregation; Platelet Aggregation - physiology; Platelets; Proteins; Proteomics; Reperfusion; Research and Analysis Methods; Troponin; United States; United States > US; Colorado
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0244792

Blood coagulation is central to myocardial ischemia and reperfusion (IR) injury. Studies on the light elicited circadian rhythm protein Period 2 (PER2) using whole body Per2-/- mice found deficient platelet function and reduced clotting which would be expected to protect from myocardial IR-injury. In contrast, intense light induction of PER2 protected from myocardial IR-injury while Per2 deficiency was detrimental. Based on these conflicting data, we sought to evaluate the role of platelet specific PER2 in coagulation and myocardial ischemia and reperfusion injury. We demonstrated that platelets from mice with tissue-specific deletion of Per2 in the megakaryocyte lineage (Per2loxP/loxP-PF4-CRE) significantly clot faster than platelets from control mice. We further found increases in infarct sizes or plasma troponin levels in Per2loxP/loxP-PF4-CRE mice when compared to controls. As intense light increases PER2 protein in human tissues, we also performed translational studies and tested the effects of intense light therapy on coagulation in healthy human subjects. Our human studies revealed that intense light therapy repressed procoagulant pathways in human plasma samples and significantly reduced the clot rate. Based on these results we conclude that intense light elicited PER2 has an inhibitory function on platelet aggregation in mice. Further, we suggest intense light as a novel therapy to prevent or treat clotting in a clinical setting.