DIASTOLIC FUNCTION ASSOC W/ WHOLE-BODY PALMITATE OXIDATION, SERUM HDL IN HIV+

HIV 中的舒张功能关联与全身棕榈酸氧化、血清 HDL

• 批准号: 7721458
• 负责人: TODD CADE
• 金额: $ 0.98万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721458
• 关键词: Anatomy; Cardiac; Computer Retrieval of Information on Scientific Projects Database; Depressed mood; EFRAC; Exercise; Exhibits; Functional disorder; Funding; Grant; HIV; HIV Infections; HIV Protease Inhibitors; High Density Lipoproteins; Institution; Kinetics; Left Ventricular Mass; Lipolysis; Methods; Nonesterified Fatty Acids; Palmitates; Protease Inhibitor; Rate; Research; Research Personnel; Resources; Rest; Serum; Source; Two-Dimensional Doppler Echocardiography; United States National Institutes of Health; base; fatty acid oxidation; indexing; lipid metabolism; oxidation; pressure

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. Objectives: HIV and protease inhibitor (PI)-based ART are associated with abnormal lipid metabolism and diastolic dysfunction. We used submaximal exercise to stimulate whole-body lipolysis and free fatty acid (FFA) oxidation and examined relationships among FFA kinetics, resting cardiac function, and PI use in HIV+ taking PI (ritonavir¿)-based ART (HIV+PI), HIV+ taking NRTI-based ART (HIVnoPI), and HIV-negative controls (Ctrl). We hypothesized that HIV+PI would have higher lipolytic rates and lower FFA oxidation rates during rest and exercise than HIVnoPI and Ctrl, and that FFA kinetics would be associated with abnormalities in cardiac function. Methods. 1-13C palmitate was infused during rest and 70min of submaximal exercise (50% peakVO2) to quantify basal and exercise-stimulated lipolytic rate (PalmRa) and palmitate oxidation rate (PalmOx) in 3 groups: HIV+PI (n=10), HIVnoPI (n=9), and Ctrl (n=5). Resting 2-D and Doppler echocardiography was used to quantify cardiac contractile and anatomic parameters. Results: In contrast to our hypothesis, PalmRa was similar among the 3 groups during rest and exercise. Resting PalmOx was higher in HIV+PI (1.0 ¿ 0.5, p<0.05) than Ctrl (0.4 ¿ 0.1), but was not different between Ctrl and HIVnoPI (0.8 ¿ 0.4 mmol/kgFFM/min). When HIV+ groups were combined, PalmOx during rest (0.9 ¿ 0.4 vs. 0.4 ¿ 0.1) and during exercise (2.0 ¿ 0.9 vs. 0.8 ¿ 0.4 mmol/kgFFM/min, p<0.03) were higher than Ctrl. HIV+ subjects exhibited lower early diastolic velocity (global em: 12.0 ¿ 4.0 vs. 16.4 ¿ 3.8 m/s, p<0.02) and peak early (E) to peak late (A) diastolic flow velocity ratio (E/A ratio: 1.4 ¿ 0.4 vs. 2.1 ¿ 0.5, p<0.001) while left ventricular mass index (LVMI) tended to be greater (97.1 ¿ 14.4 vs. 86.1 ¿ 6.2 g/m2, p<0.09) than Ctrl. PalmOx during exercise was related to LVMI (r=0.46, p<0.05). Serum high-density lipoprotein (HDL) levels were positively related to global em (r=0.58, p<0.003), ejection fraction (r=0.37, p<0.08), flow propagation (r=0.56, p<0.006), E (r=0.44, p<0.03), E/A (r=0.55, p<0.006) and negatively related to mean arterial pressure (r= - 0.49, p<0.02) and diastolic BP (r= - 0.49, p<0.02). Conclusion: HIV infection regardless of PI use was associated with elevated whole-body FFA oxidation rates during rest and exercise. Elevated FFA oxidation and lower serum HDL levels were predictive of depressed cardiac, specifically diastolic, function.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 目的：HIV 和基于蛋白酶抑制剂 (PI) 的 ART 与脂质代谢异常和舒张功能障碍有关。我们使用次最大运动来刺激全身脂肪分解和游离脂肪酸 (FFA) 氧化，并检查了 FFA 动力学、静息心功能和 PI 在 HIV+ 服用 PI（利托那韦）为基础的 ART (HIV+PI)、HIV+ 服用 NRTI 为基础的 ART (HIVnoPI) 和 HIV 阴性对照 (Ctrl) 中的关系。我们假设 HIV+PI 在休息和运动期间比 HIVnoPI 和 Ctrl 具有更高的脂肪分解率和更低的 FFA 氧化率，并且 FFA 动力学将与心脏功能异常相关。方法。在休息和 70 分钟次最大运动（50% 峰值摄氧量）期间输注 1-13C 棕榈酸酯，以量化 3 组的基础和运动刺激的脂肪分解率 (PalmRa) 和棕榈酸酯氧化率 (PalmOx)：HIV+PI (n=10)、HIVnoPI (n=9) 和 Ctrl (n=5)。静息二维和多普勒超声心动图用于量化心脏收缩和解剖参数。结果：与我们的假设相反，三组在休息和运动期间的 PalmRa 相似。 HIV+PI 中的静息 PalmOx (1.0 ¿ 0.5, p<0.05) 高于 Ctrl (0.4 ¿ 0.1)，但 Ctrl 和 HIVnoPI 之间没有差异 (0.8 ¿ 0.4 mmol/kgFFM/min)。当 HIV+ 组合并时，休息期间的 PalmOx（0.9 ¿ 0.4 vs. 0.4 ¿ 0.1）和运动期间（2.0 ¿ 0.9 vs. 0.8 ¿ 0.4 mmol/kgFFM/min，p<0.03）均高于 Ctrl。 HIV+受试者表现出较低的早期舒张速度（总体em：12.0 ¿ 4.0 vs. 16.4 ¿ 3.8 m/s，p<0.02）和早期峰值（E）与峰值晚期（A）舒张流速比（E/A比：1.4 ¿ 0.4 vs. 2.1 ¿ 0.5，p<0.001），而左心室质量指数(LVMI) 往往更大 (97.1 ¿ 14.4 vs. 86.1 ¿ 6.2 g/m2, p<0.09) 比 Ctrl。运动期间的 PalmOx 与 LVMI 相关（r=0.46，p<0.05）。血清高密度脂蛋白（HDL）水平与总体em（r=0.58，p<0.003）、射血分数（r=0.37，p<0.08）、血流传播（r=0.56，p<0.006）、E（r=0.44，p<0.03）、E/A（r=0.55，p<0.006）呈正相关，与平均值呈负相关动脉压（r= - 0.49，p<0.02）和舒张压（r= - 0.49，p<0.02）。结论：无论是否使用 PI，HIV 感染都与休息和运动期间全身 FFA 氧化率升高相关。 FFA 氧化升高和血清 HDL 水平降低预示着心脏功能，特别是舒张功能下降。