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Acquisition of an HPLC Electrospray/chemical ionization triple quadrupole linear ion trap mass spectrometer system.

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? DESCRIPTION (provided by applicant): The purpose of this application is to request funds for acquisition of an integrated instrument system comprising an AB Sciex 6500 triple quadrupole linear ion trap mass spectrometer with an electrospray and atmospheric pressure chemical ionization source, a Parker Balston Tri Gas Generator and a Shimadzu dual pump HPLC system with autosampler, column oven and controller. This instrument system enables highly specific detection, structural identification and quantitation of naturally occurring and synthetic molecules in complex biological samples. The instrument will be used by VA funded Major Users at the Lexington VA Medical Center who share an interest in understanding how being obese or overweight increases the risk of cardiovascular disease. The investigators participating in this proposal are investigating the concept that diet- dependent obesity and consequent hyperlipidemia result in changes in the lipid composition of circulating plasma components to initiate mechanisms that promote cardiovascular disease risk. The requested instrument system is required to complete the aims of VA sponsored research that tests specific hypotheses about how diets high in fats and carbohydrates lead to the formation of cardiovascular disease promoting lipids and lipid metabolites. Other minor users who will benefit from the instrument are studying the role of bioactive lipids as mediators of stem cell mobilization and homing after a heart attack and as potential markers and therapeutic targets for diagnosis and treatment of Traumatic Brain Injury. All of these conditions are of high relevance to Veterans Health. In particular, Obesity and associated chronic health conditions cause significant morbidity and negatively impact military readiness. Sixty-one to 83% of Department of Defense healthcare beneficiaries and 78% of Veterans are overweight or obese. Treatment of diseases associated with overweight and obesity is consistent with the priorities of the leadership of the Department of Veterans Affairs t promote personalized, proactive Veteran-driven care. Obesity is associated with known risk factors for cardiovascular disease including high blood pressure, elevated plasma triglycerides and cholesterol, alterations in the balance between HDL-associated good cholesterol and LDL-associated bad cholesterol and diabetes. However, obesity predicts cardiovascular disease risk even when these co-morbid conditions are not present. Dietary restriction and exercise programs such as the VHA Move program can accomplish significant weight loss in Veterans but the majority of obese dieters fail to maintain their reduced weight. Given these challenges, a better understanding of the link between diet and cardiovascular disease risk that will result from completion of these studies might lead to improvements in healthful nutrition for obese or overweight veterans or identify targets for pharmacological intervention to mitigate cardiovascular disease risk associated with obesity in Veterans and active duty military personnel. The requested instrument is essential for completion of our research in this important area.

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