Figure 5. Critical role of MOPr for endothelial phenotype, proliferation, and signaling.
(A) Endothelial cell morphology of BOECs isolated from WT (left panel) and MOPr-KO (right panel) mice. (B) BOEC proliferation was quantified after treatment with MOPr agonists (morphine/hydromorphone/fentanyl) in MOPr-KO or WT mice. (C) Morphine-induced activation of phospho-p42/p44 MAPK/ERK in BOECs from WT and MOPr-KO mice. (D) Percentage of remaining wound area was calculated after incubation of scratch wounded HDMECs in the presence or absence of morphine, MOPr antagonist MNTX, or both. *p < 0.05, $p < 0.01, #p < 0.001, †p < 0.0001. Significance was determined by t-test (B; unpaired, two-tailed) as well as two-way ANOVA with Bonferroni’s multiple comparison (D). Abbreviations: MOPr, mu-opioid receptor; BOECs, blood outgrowth endothelial cells; WT, wild-type; KO, knockout; MAPK/ERK, mitogen activated protein kinase/extracellular signal regulated kinase; MNTX, methylnaltrexone.