Study of Platelet Hyperactivity and Vascular Remodeling in Overweight and Obese A

超重和肥胖患者血小板亢进与血管重塑的研究

• 批准号: 8056229
• 负责人: Jennifer N. Cooper
• 金额: $ 4.18万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8056229
• 关键词: Adult; Aldosterone; Alleles; Antiplatelet Drugs; Arterial Fatty Streak; Atherosclerosis; Blood Platelets; Blood Vessels; Body Size; Body Weight decreased; Cardiovascular Diseases; Cardiovascular system; Cells; Chronic; Clinical; Diet; Dietary Sodium; Disease; Disease Progression; Enzyme Immunoassay; Event; Excretory function; Functional disorder; Genetic; Genetic Polymorphism; Hyperactive behavior; In Vitro; Individual; Inflammation; Inflammatory; Insulin; Insulin Resistance; Intake; Integrin alpha2; Integrin beta3; Intervention; Intervention Trial; Lead; Leptin; Life Style; Light; Link; Measures; Metabolic syndrome; Morbidity - disease rate; Obesity; Overweight; Oxidative Stress; Participant; Physical activity; Physiologic pulse; Physiological; Plasma; Platelet Activation; Platelet aggregation; Play; Process; Randomized Clinical Trials; Receptor Gene; Reporting; Risk; Risk Factors; Role; Single Nucleotide Polymorphism; Sodium; Sodium Chloride; Thick; Thrombosis; Thrombus; Time; United States; Variant; Vascular remodeling; Visit; Weight; Weight Gain; atherogenesis; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular risk factor; experience; follow-up; improved; in vivo; intima media; lifestyle factors; lifestyle intervention; mortality; receptor; response; salt sensitive; urinary; waist circumference; young adult

DESCRIPTION (provided by applicant): Cardiovascular diseases (CVDs) are the leading causes of morbidity and mortality in the United States and throughout the developed world. CVDs share a common pathophysiology - atherosclerosis. Atherosclerosis is a chronic inflammatory disease influenced by circulating cells, including platelets. Platelets play a central role not only in the process of thrombus formation, but also in atherogenesis and the progression of atherosclerotic lesions. Platelet hyperactivity is likely an important factor in the progression of subclinical cardiovascular disease (CVD) in healthy adults. Obesity and dietary sodium are two factors that have been linked to both CVD and altered platelet function. Obese individuals have an increased risk of thrombosis, which may be partially explained by platelet hyperactivity. It has also been suggested that obese individuals are more salt-sensitive than normal weight individuals, which may place them at an increased risk for negative cardiovascular changes associated with a high salt diet. It is proposed that lifestyle changes, such as weight loss and reduced dietary sodium, reduce platelet hyperactivity in obese individuals. The proposed project aims to assess in vivo platelet hyperactivity in overweight and obese participants in a lifestyle intervention trial evaluating the effects of weight loss, increased physical activity, and sodium restriction on vascular remodeling (R01 HL077525-04). Although both obesity and high dietary sodium have been linked to in vitro platelet hyperactivity, these factors' and other CVD risk factors' associations with in vivo platelet activation remain unclear, as does the extent to which genetics influences in vivo platelet activation in healthy individuals. The proposed project will measure in vivo platelet activation as plasma 2-thromboglobulin (2-TG) using an enzyme immunoassay. 2-TG is released specifically by platelets only upon their activation. Plasma markers of in vivo platelet activity, such as 2-TG, are easily measured and accurately reflect basal levels of platelet activity. The proposed project will identify whether in vivo platelet hyperactivity (high 2-TG) is associated with dietary sodium, CVD risk factors, measures of vascular adaptation, and whether several functional polymorphisms in platelet receptor genes influence in vivo activation and vascular adaptation. The specific aims of this project are to determine, in an overweight/obese population, (1) whether in vivo platelet hyperactivity is positively associated with dietary sodium intake (2) which CVD risk factors are associated with platelet hyperactivity (3) if in vivo platelet hyperactivity is positively associated with measures of subclinical CVD or their rates of change and (4) whether functional variants in platelet receptor genes influence in vivo platelet activation and subclinical CVD measures. By shedding light on the determinants of platelet hyperactivity and its role in vascular remodeling, this project will improve our ability to target currently healthy overweight and obese adults for appropriate lifestyle changes for primary CVD prevention, thereby contributing to reducing the burden of CVD experienced by overweight and obese individuals. PUBLIC HEALTH RELEVANCE: This project will identify genetic, physiologic, and lifestyle factors associated with elevated platelet activity and vascular remodeling in healthy overweight and obese adults. In particular, lifestyle changes such as weight loss and dietary sodium reduction will be evaluated for their abilities to reduce the platelet hyperactivity found in obese individuals. Because platelets are a key culprit in cardiovascular disease, this project will contribute to our understanding of how to reduce the excess cardiovascular disease risk experienced by overweight and obese individuals.

描述（由申请人提供）：心血管疾病（cvd）是美国和整个发达国家发病率和死亡率的主要原因。心血管疾病有一个共同的病理生理机制——动脉粥样硬化。动脉粥样硬化是一种受循环细胞（包括血小板）影响的慢性炎症性疾病。血小板不仅在血栓形成过程中发挥核心作用，而且在动脉粥样硬化发生和动脉粥样硬化病变的进展中也起着重要作用。血小板过度活跃可能是健康成人亚临床心血管疾病（CVD）进展的重要因素。肥胖和饮食中的钠是与心血管疾病和血小板功能改变有关的两个因素。肥胖个体血栓形成的风险增加，部分原因可能是血小板过度活跃。也有人认为，肥胖的人比正常体重的人对盐更敏感，这可能使他们在高盐饮食中患心血管疾病的风险增加。研究人员提出，生活方式的改变，如减肥和减少饮食中的钠，可以减少肥胖个体的血小板过度活跃。该项目旨在评估生活方式干预试验中超重和肥胖参与者体内血小板活性过高，评估减肥、增加体力活动和限制钠对血管重塑的影响（R01 h077525 -04）。尽管肥胖和高钠饮食都与体外血小板过度活跃有关，但这些因素和其他心血管疾病风险因素与体内血小板激活的关联尚不清楚，基因对健康个体体内血小板激活的影响程度也不清楚。拟议的项目将使用酶免疫分析法测量血浆2-血小板球蛋白（2-TG）的体内血小板活化。2-TG只有在血小板被激活时才会被特异性释放。体内血小板活性的血浆标志物，如2-TG，很容易测量并准确反映血小板活性的基础水平。拟议的项目将确定体内血小板高活性（高2-TG）是否与饮食钠、心血管疾病危险因素、血管适应措施有关，以及血小板受体基因的几种功能多态性是否影响体内激活和血管适应。该项目的具体目的是确定，在超重/肥胖人群中，(1)体内血小板过度活跃是否与饮食钠摄入量呈正相关(2)哪些心血管疾病危险因素与血小板过度活跃相关(3)体内血小板过度活跃是否与亚临床心血管疾病的测量或其变动率呈正相关(4)血小板受体基因的功能变异是否影响体内血小板激活和亚临床心血管疾病的测量。通过阐明血小板过度活跃的决定因素及其在血管重塑中的作用，该项目将提高我们针对当前健康超重和肥胖成人的能力，为初级心血管疾病预防提供适当的生活方式改变，从而有助于减轻超重和肥胖个体的心血管疾病负担。