Vascular endothelial growth factor receptor and coreceptor expression in human acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is characterized by the development of noncardiogenic pulmonary edema, which has been related to the bioactivity of vascular endothelial growth factor (VEGF). Vascular endothelial growth factor receptors and coreceptors regulate this bioactivity. We hypothesized VEGF receptors 1 and 2 (VEGFR1, VEGFR2) and coreceptor neuropilin-1 (NRP-1) would be expressed in human lung tissue with a significant change in expression in ARDS lung.

Archival "normal" (no lung pathology and non-ARDS), "early" (within 48 hours), and "later" (after day 7) ARDS lung-tissue sections (n = 5) were immunostained for VEGFR1, VEGFR2, and NRP-1 from human subjects (n = 4). Staining was assessed densitometrically using Histometrix software.

VEGFR1, VEGFR2, and NRP-1 were expressed on both sides of the alveolar-capillary membrane in both normal and ARDS human lung tissue. In later ARDS, there was a significant up-regulation of VEGFR1 and VEGFR2 versus normal and early ARDS (P < .0001). Neuropilin-1 was down-regulated in early ARDS versus normal lung (P < .05), with normalization in later ARDS (P < .001).

Differential temporal VEGFR1, VEGFR2, and NRP-1 up-regulation occurs in human ARDS, providing evidence of further functional regulation of VEGF bioactivity via VEGFR2 consistent with a protective role for VEGF in lung injury recovery. The mechanisms behind these observations remain to be clarified.