Changes of Sequestered Leukocytes and Platelets by Inhalation Prostaglandin E&lt;sub&gt;1&lt;/sub&gt; in the Pulmonary Microvasculature of Rats with Monocrotaline-Induced Pulmonary Hypertension

Kato, Shiro; Kishiro, Izumi; Sugimura, Hiroyuki; Machida, Suguru; Fuse, Daisuke; Kaneko, Noboru

doi:10.1159/000048996

Cited by 2 publications

(1 citation statement)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3,[7][8][9][10] On the luminal side, there is an increase in adhesiveness of the endothelial cell surface to cellular elements in the bloodstream. 15 The initial in vivo phenotypic changes in PAECs in lungs of MCT-treated rats have been extensively studied in cell culture. Briefly, within 48 hours, monocrotaline pyrrole (MCTP)-treated PAECs show a marked increase in cell size, enlarged nuclei, and increased and continuing DNA synthesis, leading to hypertetraploidy.…”

mentioning

confidence: 99%

Disruption of Endothelial-Cell Caveolin-1α/Raft Scaffolding During Development of Monocrotaline-Induced Pulmonary Hypertension

et al. 2004

View full text Add to dashboard Cite

Background-In the monocrotaline (MCT)-treated rat, there is marked stimulation of DNA synthesis and megalocytosis of pulmonary arterial endothelial cells (PAECs) within 3 to 4 days, followed by pulmonary hypertension (PH) 10 to 14 days later. Growing evidence implicates caveolin-1 (cav-1) in plasma membrane rafts as a negative regulator of promitogenic signaling. We have investigated the integrity and function of endothelial cell-selective cav-1␣/raft signaling in MCT-induced PH. Methods and Results-Although PH and right ventricular hypertrophy developed by 2 weeks after MCT, a reduction in cav-1␣ levels in the lung was apparent within 48 hours, declining to Ϸ30% by 2 weeks, accompanied by an increase in activation of the promitogenic transcription factor STAT3 (PY-STAT3). Immunofluorescence studies showed a selective loss of cav-1␣ and platelet endothelial cell adhesion molecule-1 in the PAEC layer within 48 hours after MCT but an increase in PY-STAT3. PAECs with cav-1␣ loss displayed high PY-STAT3 and nuclear immunostaining for proliferating cell nuclear antigen (PCNA). Biochemical studies showed a loss of cav-1␣ from the detergent-resistant lipid raft fraction concomitant with hyperactivation of STAT3. Moreover, cultured PAECs treated with MCT-pyrrole for 48 hours developed megalocytosis associated with hypo-oligomerization and reduction of cav-1␣, hyperactivation of STAT3 and ERK1/2 signaling, and stimulation of DNA synthesis. Conclusions-MCT-induced disruption of cav-1␣ chaperone and scaffolding function in PAECs likely accounts for diverse alterations in endothelial cell signaling in this model of PH.

show abstract

mentioning

confidence: 99%