Cranberry flavonoids and cardiovascular inflammation

描述（由申请人提供）：我们的长期目标是开发一个研究项目，研究功能性食品和营养补充剂对心血管炎症的影响，包括血管对细菌脂多糖（LPS）、高胆固醇血症和动脉粥样硬化的反应。对LPS或高胆固醇血症的血管炎症反应的许多组成部分是相似的。蔓越莓是类黄酮的膳食来源，可以减少炎症和动脉粥样硬化。具体来说，类黄酮的抗炎作用可能会降低脂多糖诱导的血管炎症、高胆固醇血症或两者兼而有之。我们将利用一种独特且高度相关的动物模型——家族性高胆固醇血症（FH）猪，确定饲喂蔓越莓黄酮对体内炎症的影响，并评估炎症细胞和对蔓越莓黄酮抗炎作用重要的生化物质。目的1：研究正常猪饲喂CJP对体内心肺炎症反应机制的影响。具体目的2：确定饲喂CJP对FH猪体内心肺炎症反应机制的影响。目的3：测定体外饲喂CJP（和静脉注射LPS）对FH和正常猪血管功能的影响。结果将提供新的信息关于功能性抗炎作用的全食物营养补充剂，CJP。这些结果将提高对相关动物模型（FH猪）中蔓越莓类黄酮与动脉粥样硬化炎症机制相互作用的理解。研究结果有望进一步研究这种全食品补充剂的细胞机制，并在未来进行临床研究和应用，以减少人类心血管炎症。

DESCRIPTION (provided by applicant): Our long term objective is to develop a research program examining effects of functional foods and nutritional supplements on cardiovascular inflammation, including vascular responses to bacterial lipopolysaccharides (LPS), hypercholesterolemia and atherosclerosis. Many components of the vascular inflammatory response to LPS or hypercholesterolemia are similar. Cranberries are a dietary source of flavonoids which may decrease inflammation and atherosclerosis. Specifically, the anti-inflammatory effects of flavonoids may decrease LPS-induced vascular inflammation, hypercholesterolemia, or both. We will determine the effects of feeding CJP on inflammation in vivo, and evaluate inflammatory cells and biochemicals important to the anti-inflammatory effects of cranberry flavonoids using a unique and highly relevant animal model, the familial hypercholesterolemic (FH) pig. Specific aim 1: Determine the effect of feeding CJP to normal pigs on cardiopulmonary inflammatory response mechanisms in vivo. Specific aim 2: Determine the effect of feeding CJP to FH pigs on cardiopulmonary inflammatory response mechanisms in vivo. Specific aim 3: Determine the effect of feeding CJP (and IV LPS) on vascular function ex vivo in FH and normal pigs. Results will provide new information regarding functional anti-inflammatory effects of a whole food nutritional supplement, CJP. These results will improve understanding of interactions of cranberry flavonoids with inflammatory mechanisms in atherosclerosis in a relevant animal model, the FH pig. Results are expected to lead to further investigation of cellular mechanisms and future clinical investigation and application of this whole food supplement to reduce cardiovascular inflammation in human beings.