Division of Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
PLoS One. 2019 Jul 31;14(7):e0220490. doi: 10.1371/journal.pone.0220490. eCollection 2019.
Pulmonary hypertension (PH) is characterized by elevated pulmonary artery pressure but classified into subgroups based on disease etiology. It is established that systemic bioenergetic dysfunction contributes to the pathogenesis of pulmonary arterial hypertension classified as World Health Organization (WHO) Group 1. Consistent with this, we previously showed that platelets from Group 1 PH patients demonstrate increased glycolysis and enhanced maximal capacity for oxidative phosphorylation, which is due to increased fatty acid oxidation (FAO). However, it remains unclear whether identical mitochondrial alterations contribute to the pathology of other PH subgroups. The most prevalent subgroup of PH is WHO Group 2, which encompasses pulmonary venous hypertension secondary to left heart disease. Here, we hypothesized that platelets from Group 2 subjects show bioenergetic alteration compared to controls, and that these changes were similar to Group 1 PH patients.
We isolated platelets from subjects with Group 2 PH and controls (n = 20) and measured platelet bioenergetics as well as hemodynamic parameters. We demonstrate that Group 2 PH platelets do not show a change in glycolytic rate but do demonstrate enhanced maximal capacity of respiration due at least partially to increased FAO. Moreover, this enhanced maximal capacity correlates negatively with right ventricular stroke work index and is not changed by administration of inhaled nitrite, a modulator of pulmonary hemodynamics.
These data demonstrate that Group 2 PH subjects have altered bioenergetic function though this alteration is not identical to that of Group 1 PH. The implications of this alteration for disease pathogenesis will be discussed.
肺动脉高压（PH）的特征是肺动脉压升高，但根据病因学可分为亚组。已经证实，全身生物能量功能障碍有助于肺动脉高压的发病机制，被归类为世界卫生组织（WHO）第 1 组。与此一致，我们之前表明，第 1 组 PH 患者的血小板表现出增加的糖酵解和增强的氧化磷酸化最大能力，这是由于增加的脂肪酸氧化（FAO）所致。然而，目前尚不清楚相同的线粒体改变是否会导致其他 PH 亚组的病理变化。PH 最常见的亚组是 WHO 第 2 组，包括继发于左心疾病的肺静脉高压。在这里，我们假设与对照组相比，第 2 组患者的血小板表现出生物能量改变，并且这些改变与第 1 组 PH 患者相似。
我们从第 2 组 PH 患者和对照组（n=20）中分离血小板，并测量血小板生物能量以及血液动力学参数。我们表明，第 2 组 PH 血小板的糖酵解速率没有变化，但表现出呼吸最大能力增强，至少部分原因是 FAO 增加。此外，这种增强的最大能力与右心室搏动工作指数呈负相关，并且不受吸入亚硝酸盐的影响，亚硝酸盐是一种调节肺血液动力学的调节剂。
这些数据表明，第 2 组 PH 患者存在生物能量功能改变，但这种改变与第 1 组 PH 患者的改变并不完全相同。将讨论这种改变对疾病发病机制的影响。
