ATHEROSCLEROTIC CARDIOVASCULAR DISEASE (CVD) IS A CHRONIC INFLAMMATORY DISEASE, INITIATED BY ENDOTHELIAL DAMAGE AND PROMOTED BY A NUMBER OF CELL TYPES TO INCLUDE PLATELET ACTIVATION. THERAPEUTIC REDUCTION OF CARDIOVASCULAR DISEASE PROGRESSION AND EVENTS HAS INCLUDED LIMITING PLATELET ACTIVATION THROUGH INHIBITION OF CYCLOOXYGENASE (COX) WITH ASPIRIN, WHICH REDUCES THE PRODUCTION OF THE KNOWN PLATELET ACTIVATOR THROMBOXANE, ONE OF MANY BIOACTIVE LIPIDS THAT ARE COLLECTIVELY KNOWN AS OXYLIPINS. OLIVE OIL HAS LONG BEEN CONSIDERED A KEY COMPONENT OF A MEDITERRANEAN DIETARY PATTERN, YET ONLY RECENTLY HAS THIS EFFECT BEEN DIRECTLY DEMONSTRATED FOR THE PRIMARY PREVENTION OF CVD. OF PARTICULAR INTEREST IS THE OBSERVATION THAT THE INCORPORATION OF PHENOLIC-RICH EXTRA VIRGIN OLIVE OIL (EVOO) INTO A MEDITERRANEAN DIETARY PATTERN FOR CLOSE TO 5 YEARS REDUCED PRIMARY CVD EVENTS. EVOO PROVIDES A NUMBER OF PHENOLICS AND POLYPHENOLS THAT MAY BE OF BENEFIT. IN 2011 THE EUROPEAN FOOD SAFETY AUTHORITY (EFSA) ISSUED GUIDANCE FOR HEALTH CLAIMS TOWARDS THE PREVENTION OF LDL OXIDATION. FOR THIS CLAIM, AN OLIVE OIL MUST CONTAIN 5 MG OF HYDROXYTYROSOL AND ITS DERIVATIVES (E.G. OLEUROPIEN COMPLEX AND TYROSOL), AS THE OIL IS CONSUMED DAILY WITHIN THE CONTEXT OF A BALANCED DIET. IT IS IMPORTANT TO NOTE THAT THIS DEFINITION CAN LEND TOWARDS A DIVERSE PHENOLIC CONTENT WITHIN ANY PARTICULAR OIL. EVOOS CONTAIN AN ARRAY OF AT LEAST 30 PHENOLIC COMPOUNDS, WHICH HAVE DEMONSTRATED ANTIOXIDANT AND ANTI-INFLAMMATORY PROPERTIES. IN DIETARY INTERVENTION TRIALS, ANTI-PLATELET AND ANTI-INFLAMMATORY EFFECTS HAVE BEEN OBSERVED AFTER THE INTAKE OF EVOO OR VIRGIN OLIVE OIL (VOO). IN ADDITION, HIGH PHENOLIC EVOO HAS BEEN OBSERVED TO PROVIDE GREATER PROTECTION COMPARED TO EITHER EVOOS OR VOOS THAT ARE LOWER IN PHENOLIC CONTENT OR REFINED OLIVE OILS SUGGESTING THE IMPORTANCE OF TOTAL PHENOLIC CONTENT. HOWEVER, WHILE THESE TRIALS FOCUSED ON THE TOTAL PHENOLIC CONTENT TOWARDS CARDIOPROTECTION, INFORMATION ON THE SPECIFIC PHENOLIC CONTENT OF EVOO IS OFTEN UNKNOWN.WE HAVE RECENTLY COMPLETED A PROBE TRIAL AND FOUND THAT WHEN HEALTHY MALE ADULTS WERE PROVIDED WITH 3 DIFFERENT EVOOS, EACH MATCHED IN PHENOLIC CONTENT BUT WITH A DISTINCT PHENOLIC PROFILE, A REDUCTION IN PLATELET AGGREGATION WAS OBSERVED 2 HOURS POST-INGESTION OF OILS RICH IN THE EVOO PHENOLIC OLEOCANTHAL. OF PARTICULAR INTEREST WAS THE CONSIDERABLE INDIVIDUAL VARIABILITY IN BOTH PLATELET AGGREGATION AND LIPID MEDIATOR RESPONSES. THIS VARIABILITY IS REMINISCENT OF THE VARIABILITY OBSERVED WITH ASPIRIN INTAKE, AND MAY BE EXPLAINED THROUGH A COMBINATION OF GENETIC AND DIETARY FACTORS INFLUENCING EITHER THE AGGREGATION RESPONSE ITSELF OR THE METABOLISM OF EVOO BIOACTIVES. IN THE CURRENT PROPOSAL, WE TO SEEK TO FURTHER DEFINE THE INFLUENCE OF PHENOLIC PROFILE ON PLATELET SIGNALING.TO ACHIEVE THIS, WE WILL FIRST DETERMINE THE TIME DEPENDENCE OF THE ACUTE PLATELET AGGREGATION RESPONSE 2-6 HOURS AFTER THE INTAKE OF OLEOCANTHAL-RICH EVOO. THIS WILL BE FOLLOWED BY AN EXPLORATION OF THE ACUTE AND SHORT-TERM (2 WEEKS OF DAILY INTAKE) PLATELET RESPONSE IN HEALTHY ADULTS WITH DAILY OLEOCANTHAL-RICH EVOO INTAKE. WITHIN THIS STUDY WE WILL EXAMINE THE EFFECTS OF EVOO INTAKE ON A NUMBER OF KEY PLATELET ACTIVATION MARKERS AND INTRACELLULAR SIGNALING PATHWAYS NOT MEASURED IN THE ORIGINAL TRIALS. FINALLY WE WILL ALSO SEEK TO FURTHER DEFINE POTENTIAL VARIANCE IN RESPONSE USING A SYSTEMS BIOLOGY APPROACH THAT MODELS AN INDIVIDUAL'S: 1) TYPICAL DIETARY INTAKE TO THEIR PHYSIOLOGICAL RESPONSE TO PLATELET ACTIVATION; 2) THE PRODUCTION OF BIOACTIVE LIPID MEDIATORS FROM OLEOCANTHAL-RICH EVOO INTAKE; 3) METABOLOMICS PROFILE AFTER THE ACUTE INTAKE OF EVOO PHENOLICS.