Quantifying the effect of obesity and comorbid hypertension on cardiac function

量化肥胖和合并高血压对心功能的影响

• 批准号: 8911342
• 负责人: MORIEL VANDSBURGER
• 金额: $ 27.09万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8911342
• 关键词: Adult; Affect; Animals; Antihypertensive Agents; Blood Pressure; Cardiac; Cardiac Function Study; Cardiovascular Diseases; Child; Clinic; Computer software; Data; Development; Diet; Fat-Restricted Diet; Fatty acid glycerol esters; Functional disorder; Heart; Heart Hypertrophy; Human; Hydralazine; Hypertension; Hypertrophy; Image; Kentucky; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mediating; Mus; Myocardial; Myocardial Contraction; Myocardial dysfunction; Obese Mice; Obesity; Obesity Related Hypertension; Patients; Pharmaceutical Preparations; Protocols documentation; Public Health; Relaxation; Research; Role; Technology; Time; Translating; Translations; United States; Universities; Weight; Work; cardiovascular risk factor; feeding; heart function; mortality; mouse model; normotensive; obesity in children; western diet

Obesity is a major public health problem affecting over one third of adults in the United States and one in five children. Obesity is related to an increased risk of cardiovascular mortality, which may in part be mediated through a direct effect on the heart leading to dysfunction. However, the time course over which obesity leads to cardiac dysfuncfion, the underlying mechanisms of myocardial dysfunction in obesity, and potential treatments have not been fully elucidated. Our preliminary data ufilizing cardiac magnefic resonance imaging (MRI) show abnormalifies in the magnitude of contracfion, synchrony of contraction, and myocardial mass in the hearts of mice fed a high-fat Western diet. The objective of this project is to define the time course over which this dysfunction occurs in mice, evaluate the role of hypertension in the development of this dysfunction, and to translate this work into humans by determining whether children in our pediatric obesity clinic have evidence of cardiac dysfunction. This project has 3 specific aims as follows: 1) Determine the time course over which myocardial dysfunction develops in mice fed a high-fat Western diet. We will quantify advanced measures of cardiac function assessing mass, contraction and relaxation and synchrony overtime in a longitudinal study using magnetic resonance imaging. 2) Determine the effect of anti-hypertensive therapy on the development of hypertrophy and cardiac dysfunction in mice fed a high-fat Western diet. Mice on a high-fat Western diet develop obesity-related hypertension that is reversible with anti-hypertensive therapy. However, the effect of anti-hypertensive therapy on cardiac function in obese mice has not been studied and may elucidate underiying mechanisms. We will compare cardiac function measured in the'mice on a high-fat Western diet in specific aim 1 to a group of mice on a high-fat Western diet and hydralazine. 3) Quantify cardiac function in children with obesity using advanced MRI. State-of-the-art technology at the University of Kentucky enables us to directly translate our findings in mice into our pediatric obesity clinic with over 800 patients. The effect of obesity on myocardial function in children is largely unknown.

Obesity is a major public health problem affecting over one third of adults in the United States and one in five children. Obesity is related to an increased risk of cardiovascular mortality, which may in part be mediated through a direct effect on the heart leading to dysfunction. However, the time course over which obesity leads to cardiac dysfuncfion, the underlying mechanisms of myocardial dysfunction in obesity, and potential treatments have not been fully elucidated. Our preliminary data ufilizing cardiac magnefic resonance imaging (MRI) show abnormalifies in the magnitude of contracfion, synchrony of contraction, and myocardial mass in the hearts of mice fed a high-fat Western diet. The objective of this project is to define the time course over which this dysfunction occurs in mice, evaluate the role of hypertension in the development of this dysfunction, and to translate this work into humans by determining whether children in our pediatric obesity clinic have evidence of cardiac dysfunction. This project has 3 specific aims as follows: 1) Determine the time course over which myocardial dysfunction develops in mice fed a high-fat Western diet. We will quantify advanced measures of cardiac function assessing mass, contraction and relaxation and synchrony overtime in a longitudinal study using magnetic resonance imaging. 2) Determine the effect of anti-hypertensive therapy on the development of hypertrophy and cardiac dysfunction in mice fed a high-fat Western diet. Mice on a high-fat Western diet develop obesity-related hypertension that is reversible with anti-hypertensive therapy. However, the effect of anti-hypertensive therapy on cardiac function in obese mice has not been studied and may elucidate underiying mechanisms. We will compare cardiac function measured in the'mice on a high-fat Western diet in specific aim 1 to a group of mice on a high-fat Western diet and hydralazine. 3) Quantify cardiac function in children with obesity using advanced MRI. State-of-the-art technology at the University of Kentucky enables us to directly translate our findings in mice into our pediatric obesity clinic with over 800 patients. The effect of obesity on myocardial function in children is largely unknown.