EFFECTS OF CHRONIC GREEN TEA FLAVONOID SUPPLEMENTATION ON BIOMARKERS OF OXIDATI

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To gather data on 'the differences in disease-related biochemical markers in adult patients with lower extremity atherosclerotic disease (LEAD) with type 2 diabetes vs non-diabetics' to estimate variations in proposed measures and sample sizes of the larger planned study. Specific Aims: 1. In atheromatous plaque obtained from lower extremity arteries of adult patients with type 2 diabetes vs non-diabetics, determine the differences among tissue levels and types of biochemical markers, modulators, and receptors of inflammation and oxidative stress (eg, nitric oxide synthase and cyclooxygenase), and the histologic architecture;2. In blood samples of adult patients with LEAD with type 2 diabetes vs non-diabetics, determine the differences among levels and types of biochemical markers, modulators, and receptors of inflammation and oxidative stress (eg, nitric oxide synthase and cyclooxygenase) in leukocytes and platelets, and the quantities of 'collagen and thrombin' activated (COAT) platelets;3. In the serum and urine of adult patients with LEAD with type 2 diabetes vs non-diabetics, determine the differences among levels of biochemical markers of inflammation, oxidative stress (eg, CRP, IL-6, TNF-?, CAP-37), and cardiovascular risk (eg, A1C, lipid profile, urine microalbumin).Research Design and Methods: A cross-sectional research design (N = 40; 20 type 2 diabetic and 20 nondiabetic, 10 male and 10 female in each group) will allow for the determination of the differences and the examination of the relationship among biochemical markers, modulators, and receptors of inflammation and oxidative stress, in atheromatous plaques of lower extremities, and in leukocytes and platelets obtained from blood samples, and serum inflammatory and cardiovascular risk markers, after controlling for vascular risk factors and other co morbidities in patients with LEAD with type 2 diabetes vs non-diabetics. Atheromatous plaque, blood and urine samples will be obtained from patients with LEAD, who undergo elective atherectomy in the peripheral intervention catheterization laboratory of Presbyterian Tower (OU Medical Center). Biochemical markers, modulators, and receptors of inflammation and oxidative stress will be assessed in plaques, platelets and leukocytes, and markers of inflammation and cardiovascular risk will be measured in the serum of these patients. Histologic examination of the plaque will be performed as well. Clinical Significance: Type 2 diabetes is most strongly associated with diffuse and distal (i.e., femoropopliteal and tibial) atherosclerotic processes, causing intermittent claudication (IC) or chronic critical limb ischemia (CCLI); whereas, other LEAD risk factors (e.g., smoking and hypertension) are associated with more proximal disease in the aorto-iliofemoral vessels. CCLI is a major risk factor for lower-extremity amputation and excess mortality in patients with diabetes. Identifying the diabetes-related changes of inflammation and oxidative stress in atheroma, platelets, and leukocytes, and biochemical markers of inflammation, oxidative stress and cardiovascular risk in circulation and urine independent of vascular risk factors and co morbidities will provide pertinent insight reflecting the unique contribution of the inflammation, oxidative stress, and the circulating inflammatory & cardiovascular risk markers in underlying pathophysiological processes of LEAD in diabetes vs non-diabetics. This understanding of the pathophysiologic mechanisms in diabetes will facilitate development of novel preventive and/or therapeutic interventions for atherosclerosis in diabetes.