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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。目的：基于HIV和蛋白水解酶抑制物(PI)的抗逆转录病毒治疗与脂代谢异常和舒张期功能障碍有关。我们使用次极量运动来刺激全身脂肪分解和游离脂肪酸(FFA)氧化，并研究了HIV+服用基于利托那韦的抗逆转录病毒药物(HIV+PI)、HIV+服用基于NRTI的ART(HIVnoPI)和HIV阴性对照组(Ctrl)的FFA动力学、静息心功能和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有更高的脂解率和更低的FFA氧化率，FFA动力学与心功能异常有关。方法：研究方法。在静息状态和亚极量运动(50%PeakVO2)70min时注入1-13C棕榈酸酯，以定量测定HIV+PI组(n=10)、HIVnoPI组(n=9)和Ctrl组(n=5)的基础和运动刺激的脂解率(PalmRa)和棕榈酸酯氧化率(PalmOx)。应用静息二维超声心动图和多普勒超声心动图测量心脏收缩和解剖参数。结果：与我们的假设相反，休息和运动时3组的PalmRa相似。静息PalmOx在HIV+PI组(1.0±0.5，p&lt；0.05)高于Ctrl组(0.4±0.1)，但Ctrl组与HIVnoPI组(0.8±0.4 mmol/kgFFM/min)无差异。当HIV+组合并时，安静时PalmOx(0.9±0.4比0.4±0.1)和运动时PalmOx(2.0±0.9比0.8±0.4 mmol/kgFFM/min，p&lt；0.03)均高于Ctrl。HIV感染者的舒张期早期血流速度(Em：12.0±4.0vs.16.4±3.8m/S，p&lt；0.02)和峰早/峰晚期(E/A比值：1.4vs.2.1±0.5，p&lt；0.001)明显低于对照组(97.1vs.86.1±6.2g/m2，p&lt；0.09)。运动中的PalmOx与LVMI呈正相关(r=0.46，p&lt；0.05)。血清高密度脂蛋白水平与平均动脉压(r=-0.49，p&lt；0.003)、平均动脉压(r=-0.49，p&lt；0.02)、舒张压(r=-0.49，p&lt；0.006)、舒张压(r=-0.49，p&lt；0.006)呈负相关。0.02)。结论：无论是否使用PI，HIV感染都与休息和运动时全身FFA氧化率升高有关。升高的FFA氧化和较低的血清高密度脂蛋白水平预示着心脏功能，特别是舒张期功能的下降。

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.