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Enzymatically oxygenated phospholipids (eoxPL) formed by lipoxygenases (LOX) and cyclooxygenase (COX) in platelets and leukocytes are pro-coagulant in multiple model systems. However, their generation in arterial thrombotic disease, and how their levels are modulated by common therapies is unknown. Here, eoxPL were first characterized in isolated platelets and leukocytes from an arterial vascular disease cohort, a healthy cohort administered low dose aspirin, and from retrieved human arterial thrombi. In both cohorts, aspirin reduced platelet COX-1-derived eoxPL, while elevating diacyl 12-LOX-derived eoxPL in males, through enhanced Lands’ cycle esterification. Conversely, P2Y12 inhibition reduced 12-LOX-derived eoxPL in leukocytes. Complex aspirin-dependent gender and seasonal effects on platelet eoxPL were seen in healthy subjects. Limb or coronary (STEMI) thrombi showed a platelet eoxPL signature while carotid thrombi had a white cell profile. Mice genetically lacking leukocyte 12/15-LOX, which are deficient in eoxPL, generated smaller carotid thrombi in vivo. In summary, pro-coagulant eoxPL generation is altered in human arterial vascular disease by commonly used cardiovascular therapies. These changes to the phospholipid composition of blood cells in humans at risk of thrombotic events may be clinically significant where the pro-coagulant membrane plays a central but poorly understood role in driving elevated thrombotic risk.Key PointseoxPL generation is altered in health and arterial vascular disease by aspirin or P2Y12 inhibitors, and shows gender and seasonal variation.Aspirin regulates eoxPL by inhibiting cyclooxygenase and modulating Lands’ cycle.The eoxPL profile of human arterial thrombi identifies platelet and leukocyte involvement.Mice deficient in LOX-derived eoxPL form smaller arterial thrombiin vivo.

AimPaleoclimate reconstructions have enhanced our understanding of how past climates may have shaped present-day biodiversity. We hypothesize that habitat stability in historical Afrotropical refugia played a major role in the habitat suitability and persistence of chimpanzees (Pan troglodytes) during the late Quaternary. We aimed to build a dynamic model of changing habitat suitability for chimpanzees at fine spatio-temporal scales to provide a new resource for understanding their ecology, behaviour and evolution.LocationAfrotropics.TaxonChimpanzee (Pan troglodytes), including all four subspecies (P. t. verus, P. t. ellioti, P. t. troglodytes, P. t. schweinfurthii).MethodsWe used downscaled bioclimatic variables representing monthly temperature and precipitation estimates, historical human population density data and an extensive database of georeferenced presence points to infer chimpanzee habitat suitability at 62 paleoclimatic time periods across the Afrotropics based on ensemble species distribution models. We mapped habitat stability over time using an approach that accounts for dispersal between time periods, and compared our modelled stability estimates to existing knowledge of Afrotropical refugia. Our models cover a spatial resolution of 0.0467 degrees (approximately 5.19 km2 grid cells) and a temporal resolution of every 1,000–4,000 years dating back to the Last Interglacial (120,000 BP).ResultsOur results show high habitat stability concordant with known historical forest refugia across Africa, but suggest that their extents are underestimated for chimpanzees. We provide the first fine-grained dynamic map of historical chimpanzee habitat suitability since the Last Interglacial which is suspected to have influenced a number of ecological-evolutionary processes, such as the emergence of complex patterns of behavioural and genetic diversity.Main ConclusionsWe provide a novel resource that can be used to reveal spatio-temporally explicit insights into the role of refugia in determining chimpanzee behavioural, ecological and genetic diversity. This methodology can be applied to other taxonomic groups and geographic areas where sufficient data are available.