Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Department of Pulmonary, Allergy, and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, Ohio.
Am J Physiol Lung Cell Mol Physiol. 2020 Mar 1;318(3):L562-L569. doi: 10.1152/ajplung.00389.2019. Epub 2020 Feb 5.
Group 1 pulmonary hypertension (PH), i.e., pulmonary arterial hypertension (PAH), is associated with a metabolic shift favoring glycolysis in cells comprising the lung vasculature as well as skeletal muscle and right heart. We sought to determine whether this metabolic switch is also detectable in circulating platelets from PAH patients. We used Seahorse Extracellular Flux to measure bioenergetics in platelets isolated from group 1 PH (PAH), group 2 PH, patients with dyspnea and normal pulmonary artery pressures, and healthy controls. We show that platelets from group 1 PH patients exhibit enhanced basal glycolysis and lower glycolytic reserve compared with platelets from healthy controls but do not differ from platelets of group 2 PH or dyspnea patients without PH. Although we were unable to identify a glycolytic phenotype unique to platelets from PAH patients, we found that platelet glycolytic metabolism correlated with hemodynamic severity only in group 1 PH patients, supporting the known link between PAH pathology and altered glycolytic metabolism and extending this association to ex vivo platelets. Pulmonary artery pressure and pulmonary vascular resistance in patients with group 1 PH were directly associated with basal platelet glycolysis and inversely associated with maximal and reserve glycolysis, suggesting that PAH progression reduces the capacity for glycolysis even while demanding an increase in glycolytic metabolism. Therefore, platelets may provide an easy-to-harvest, real-time window into the metabolic shift occurring in the lung vasculature and represent a useful surrogate for interrogating the glycolytic shift central to PAH pathology.
1 组肺动脉高压（PH），即肺动脉高压（PAH），与肺血管以及骨骼肌和右心组成细胞中的糖酵解代谢转变有关。我们试图确定这种代谢转变是否也可以在 PAH 患者的循环血小板中检测到。我们使用 Seahorse 细胞外通量来测量从 1 组 PH（PAH）、2 组 PH、呼吸困难且肺动脉压正常的患者和健康对照中分离出的血小板的生物能量学。我们发现，与健康对照组相比，1 组 PH 患者的血小板表现出增强的基础糖酵解和更低的糖酵解储备，但与 2 组 PH 或无 PH 的呼吸困难患者的血小板没有区别。尽管我们无法确定 PAH 患者血小板特有的糖酵解表型，但我们发现血小板糖酵解代谢仅与 1 组 PH 患者的血流动力学严重程度相关，这支持 PAH 病理学与改变的糖酵解代谢之间的已知联系，并将这种关联扩展到体外血小板。1 组 PH 患者的肺动脉压和肺血管阻力与基础血小板糖酵解直接相关，与最大和储备糖酵解呈负相关，这表明 PAH 进展降低了糖酵解的能力，即使需要增加糖酵解代谢。因此，血小板可能为研究肺血管中发生的代谢转变提供一个易于采集的实时窗口，并代表一种有用的替代方法，用于研究 PAH 病理学核心的糖酵解转变。
