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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。目的：基于HIV和蛋白酶抑制剂（PI）的ART与脂质代谢异常和舒张功能障碍有关。我们使用次极量运动刺激全身脂肪分解和游离脂肪酸（FFA）氧化，并在HIV+服用PI（利托那韦）的ART（HIV+PI）、HIV+服用NRTI的ART（HIVnoPI）和HIV阴性对照（Ctrl）中检查FFA动力学、静息心脏功能和PI使用之间的关系。我们假设HIV+PI在休息和运动时比HIVnoPI和Ctrl具有更高的脂解率和更低的FFA氧化率，并且FFA动力学与心脏功能异常相关。方法.在休息和70分钟次极量运动（50% peakVO 2）期间输注1- 13 C棕榈酸酯，以量化3组中的基础和运动刺激的脂解率（PalmRa）和棕榈酸氧化率（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被用来量化心脏收缩和解剖参数。结果：与我们的假设相反，在休息和运动期间，3组之间的PalmRa相似。HIV+PI组静息PalmOx（1.0 <$0.5，p<0.05）高于对照组（0.4 <$0.1），但对照组和HIV无PI组之间无差异（0.8 <$0.4 mmol/kgFFM/min）。当合并HIV+组时，静息（0.9 <$0.4 vs. 0.4 <$0.1）和运动（2.0 <$0.9 vs. 0.8 <$0.4 mmol/kgFFM/min，p<0.03）期间的PalmOx高于对照组。HIV阳性受试者舒张早期血流速度较低（整体em：12.0 <$4.0 vs. 16.4 <$3.8 m/s，p<0.02）和舒张早期峰值（E）与舒张晚期峰值（A）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）倾向于大于对照组（97.1 <$14.4 vs. 86.1 <$6.2 g/m2，p<0.09）。运动时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emc呈正相关，（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 E/A（r =0.55，p<0.006）与平均动脉压（r=-0.49，p<0.02）、舒张压（r =-0.49，p<0.02）呈负相关。结论：HIV感染与PI使用无关，与休息和运动期间全身FFA氧化率升高相关。FFA氧化水平升高和血清HDL水平降低预示着心脏功能，特别是舒张功能下降。

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.