Dysfunctional endothelial cells in patients with chronic thromboembolic pulmonary hypertension

Rationale: Material obtained at pulmonary endarterectomy (PEA) offers the unique opportunity to unravel pathophysiological mechanisms underlying CTEPH. Vascular changes occurring in CTEPH might be linked to metabolic dysregulation of CTEPH endothelial cells (EC). The aim of this study was the development of an in vitro model of EC pathology using primary cultures of patient derived EC to assay cell metabolism in CTEPH. Method: Like previously showed, isolated cells from specimens collected at PEA (N=12) were confirmed as being EC. Cell migration was evaluated using scratch assay. Metabolic changes in CTEPH-EC are being studied using RT-PCR, Western-Blot and colorimetric assays. Results: CTEPH-EC showed a reduced capacity to recover from a scratch when compared with human pulmonary arterial endothelial cells (HPAE) (1-way anova, p 0.05). Conclusion: CTEPH-EC show functional impairment. Higher expression of HIF-1a is a noteworthy link with metabolic alterations. Preliminary data suggesting an increase in LDH activity can be explained, at least partially, by higher expression of HIF-1a. Variations in lactate and glucose support the presence of a metabolic pathophenotype in CTEPH-EC.