MYOCARDIAL FUNCTION AND FFA METABOLISM IN HIV-METABOLIC SYNDROME

HIV 代谢综合征中的心肌功能和 FFA 代谢

• 批准号: 7603362
• 负责人: KEVIN E YARASHESKI
• 金额: $ 2.08万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603362
• 关键词: Anti-Retroviral Agents; Appearance; Blood Circulation; Cardiac; Cardiovascular Diseases; Computer Retrieval of Information on Scientific Projects Database; Doppler Echocardiography; Dyslipidemias; Fatty Acids; Functional disorder; Funding; General Population; Grant; Heart; High Density Lipoprotein Cholesterol; Hypertriglyceridemia; Image; Institution; Insulin Resistance; Label; Left; Left Ventricular Dysfunction; Left ventricular structure; Link; Lipids; Liver; Mass Spectrum Analysis; Metabolic syndrome; Metabolism; Myocardial; Myocardium; Nonesterified Fatty Acids; Obesity; Palmitates; Pathogenesis; Positron-Emission Tomography; Radio; Rate; Reporting; Research; Research Personnel; Resources; Risk Factors; Skeletal Muscle; Source; Tissues; United States National Institutes of Health; Ventricular; Visceral; Woman; cardiovascular disorder risk; experience; men; oxidation; therapy design; uptake

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. The risk for cardiovascular disease (CVD) and left ventricular dysfunction (LVD) is greater in HIV-infected people than in the general population, but the pathogenesis is unclear. Many HIV-infected people develop metabolic syndromes (HIV+MS) that include traditional CVD and LVD risk factors (dyslipidemia, insulin resistance, visceral adiposity) that are commonly observed in HIV-seronegative people and referred to as "The Metabolic Syndrome." We have reported that HIV+MS is characterized by an elevated free fatty acid rate of appearance (FFA Ra) in the circulation (i.e., increased whole-body lipolytic rate), and lipid accumulation in skeletal muscle and liver. In HIV+MS, we hypothesize that the elevated FFA Ra increases FFA delivery, uptake and oxidation by the myocardium, but that myocardial FFA uptake eventually exceeds the ability of the heart to oxidize FFAs: intramyocardial lipid accumulation may result. We hypothesize that increased myocardial FFA uptake and oxidation are associated with structural changes in the left ventricle, and ventricular diastolic and systolic contractile dysfunction in HIV+MS. We propose to quantify whole-body FFA Ra (using 13C-palmitate and mass spectrometry), myocardial FFA delivery, uptake and oxidation (using radio-labeled palmitate and cardiac positron emission tomography (PET) imaging), and left ventricular (LV) structure, diastolic and systolic contractile function using 2-D and tissue Doppler echocardiography) in 30 HIV+MS and 30 HIV-infected people without MS. We will compare these parameters between these 2 groups, and to exactly the same parameters quantified in HIV-seronegative people with and without "The Metabolic Syndrome" who are currently being studied by co-investigators on this proposal at our Institution. For this project, HIV+MS is defined as HIV-infected women and men receiving stable anti-retroviral therapy and experiencing hypertriglyceridemia, low HDL-cholesterol levels, insulin resistance and visceral adiposity. The findings will identify similarities/differences in myocardial metabolism and LV contractile function between HIV+MS and "The Metabolic Syndrome." The findings may provide a mechanistic link between dysregulated whole-body and myocardial FFA metabolism that contributes to alterations in LV structure, contractile function and CVD. If so, treatments designed to reduce circulating FFA levels in HIV+MS, might effectively reduce CVD and LVD in HIV-infected people.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 HIV感染者的心血管疾病（CVD）和左心室功能障碍（LVD）的风险大于一般人群，但发病机理尚不清楚。 许多HIV感染者患有代谢综合征（HIV+MS），其中包括传统的CVD和LVD危险因素（血脂异常，胰岛素抵抗，内脏肥胖），通常在HIV传感器中观察到，并被称为“代谢综合征”。 我们报告说，HIV+MS的特征是循环中的游离脂肪酸外观（FFA RA）升高（即，全身脂肪溶解速率升高），骨骼肌和肝脏中的脂质积累。 在HIV+MS中，我们假设升高的FFA RA增加了心肌的FFA递送，摄取和氧化的摄取和氧化，但是心肌FFA的摄取最终超出了心脏氧化FFA的能力：心脏内心内脂质的积累可能会导致。 我们假设增加的心肌FFA摄取和氧化与左心室的结构变化有关，HIV+MS中的心室舒张压和收缩功能障碍。 We propose to quantify whole-body FFA Ra (using 13C-palmitate and mass spectrometry), myocardial FFA delivery, uptake and oxidation (using radio-labeled palmitate and cardiac positron emission tomography (PET) imaging), and left ventricular (LV) structure, diastolic and systolic contractile function using 2-D and tissue Doppler echocardiography) in 30 HIV+MS and 30没有MS的艾滋病毒感染者。 我们将在这两个组之间比较这些参数，以及与有和没有“代谢综合征”的HIV副人物中量化的完全相同的参数，他们目前正在我们机构对此提案进行共同研究的研究。 对于该项目，HIV+MS被定义为受HIV感染的男性和男性接受稳定的抗逆转录病毒疗法，患有高甘油三酸酯血症，低HDL-胆固醇水平，胰岛素抵抗和内脏肥胖。 这些发现将确定HIV+MS和“代谢综合征”之间心肌代谢和LV收缩功能的相似性/差异。 这些发现可能会提供失调的全身和心肌FFA代谢之间的机械联系，这有助于LV结构，收缩功能和CVD改变。 如果是这样，旨在降低HIV+MS中循环FFA水平的治疗方法可能会有效地减少感染HIV感染者的CVD和LVD。