RESUMEN
Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are two forms of pulmonary hypertension (PH) characterized by obstructive vasculopathy. Endothelial dysfunction along with metabolic changes towards increased glycolysis are important in PAH pathophysiology. Less is known about such abnormalities in endothelial cells (ECs) from CTEPH patients. This study provides a systematic metabolic comparison of ECs derived from CTEPH and PAH patients. Metabolic gene expression was studied using qPCR in cultured CTEPH-EC and PAH-EC. Western blot analyses were done for HK2, LDHA, PDHA1, PDK and G6PD. Basal viability of CTEPH-EC and PAH-EC with the incubation with metabolic inhibitors was measured using colorimetric viability assays. Human pulmonary artery endothelial cells (HPAEC) were used as healthy controls. Whereas PAH-EC showed significant higher mRNA levels of GLUT1, HK2, LDHA, PDHA1 and GLUD1 metabolic enzymes compared to HPAEC, CTEPH-EC did not. Oxidative phosphorylation associated proteins had an increased expression in PAH-EC compared to CTEPH-EC and HPAEC. PAH-EC, CTEPH-EC and HPAEC presented similar HOXD macrovascular gene expression. Metabolic inhibitors showed a dose-dependent reduction in viability in all three groups, predominantly in PAH-EC. A different metabolic profile is present in CTEPH-EC compared to PAH-EC and suggests differences in molecular mechanisms important in the disease pathology and treatment.
Asunto(s)
Células Endoteliales/metabolismo , Hipertensión Arterial Pulmonar/genética , Hipertensión Arterial Pulmonar/metabolismo , Embolia Pulmonar/genética , Embolia Pulmonar/metabolismo , Adulto , Anciano , Células Cultivadas , Enfermedad Crónica , Femenino , Expresión Génica , Glutamato Deshidrogenasa/genética , Glutamato Deshidrogenasa/metabolismo , Glucólisis/genética , Hexoquinasa/genética , Hexoquinasa/metabolismo , Humanos , L-Lactato Deshidrogenasa/genética , L-Lactato Deshidrogenasa/metabolismo , Masculino , Persona de Mediana Edad , Fosforilación Oxidativa , Arteria Pulmonar/citología , Piruvato Deshidrogenasa (Lipoamida)/genética , Piruvato Deshidrogenasa (Lipoamida)/metabolismoRESUMEN
OBJECTIVE: We studied patients who underwent surgical repair for total anomalous pulmonary venous return at our hospital. We report the importance of diagnosis by echocardiographic imaging before surgical treatment. METHODS: Within the period of 1990-1999, fourteen patients underwent surgical repair of this cardiopathy in our hospital. The type of anomalous drainage was supracardiac in 6 patients, infracardiac in 4, to the coronary sinus in 1, and mixed-type in 3 patients. Eleven cases were diagnosed with an echo-Doppler study, the findings being confirmed intraoperatively. RESULTS: There were 2 early deaths: one occurred in the operating room in a patient with a small left ventricle, and the second one was 35 days postoperatively as a result of a septic complication. Early in the postoperative period our primary goal has steadily been the control and treatment of pulmonary hypertension. After a mean follow-up time of 50 months, only 1 patient needed to be reoperated on and the remainder are symptomless. CONCLUSIONS: That sufficient diagnostic data on total anomalous pulmonary venous return can reliably be obtained by ultrasound scanning so that surgery can be promptly undertaken, and that its surgical risk is currently low and mid-term post-repair outcome is fairly good.
