title: Effect of nucleoprotein factor-kB (NF-κB) in endothelial cells during high blood flow-associated pulmonary vascular remodeling on vasoactive substances adrenomedullin and prostacyclin.
abstract: The aim of this study was to investigate the role of nucleoprotein factor-kB (NF-κB) on the production and secretion of vasoactive substances adrenomedullin (ADM) and prostacyclin (PGI2) by endothelial cells in a high blood flow, pulmonary hypertension in vivo model. Fifty male Wistar rats were randomly divided into four groups: 15 rats received shunt surgery (Tn group); 15 rats received shunt surgery + NF-κB inhibitor [pyrrolidine dithiocarbamate (PDTC)] (Ti group); 10 rats received sham surgery (Co group); and 10 rats were negative controls (Cn group). A left to right shunt pulmonary hypertension model was established in groups Tn and Ti. Rats in the Ti group received an intraperitoneal injection of PDTC (120 mg/kg·d) one hour before the operation for 2 weeks, and rats in the Co group were processed in the same fashion as that of the experimental groups, except that they did not undergo surgery. After 12 weeks, pulmonary artery systolic pressure was measured by cardiac catheterization, pulmonary arterial endothelial cells were isolated, and NF-κB, ADM and PGI2 protein expressions were measured in the endothelium using immunohistochemistry. ADM and PGI2 expressions were significantly lower in the Tn group relative to those of the Cn group (P<0.01) but no difference in the Ti group (P>0.05). Expressions in the Co and Cn groups were not significantly different (P>0.05). Heightened NF-κB activity in pulmonary arterial endothelial cells during high blood flow can suppress the synthesis and secretion of ADM and PGI2, potentially leading to vascular remodeling and pulmonary hypertension.
authors.affiliation: Department of Pediatrics, Qilu Hospital of Shandong University Jinan 250012, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Respiration, Chest Hospital of Xinjiang Autonomous Region Urumqi 830049, China.
authors.forename: Weina
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Qilu Hospital of Shandong University Jinan 250012, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Dong
authors.affiliation: Department of Pediatrics, Qilu Hospital of Shandong University Jinan 250012, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Xinjiang Medical University Urumqi 830054, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Luo
keywords: NF-κB; PDTC; pulmonary vascular remolding; vascular endothelial cell