Expression of pulmonary VEGF family declines with age and is further down-regulated in lipopolysaccharide (LPS)-induced lung injury

Vascular endothelial growth factor (VEGF) is a survival factor in endothelial cells and a promoter of angiogenesis that reportedly plays a pivotal role protecting against injury. In aged humans and animals, lung injuries are generally more serious and cause higher mortality. We thus hypothesized that the expression of VEGF and its related molecules in the lung declines with age. In this study, we first examined the expression of VEGF family (VEGF-A, -B, -C and -D), VEGF-A isoforms (VEGF120, 164, 188), and VEGF-specific receptors (VEGFR-1: Flt-1; VEGFR-2: Flk-1 and VEGFR-3: Flt-4) by quantitative RT-PCR in lungs from young and old mice. Expression of all these except for VEGF-D was significantly lower in old mice than in young mice. We then subjected young and old mice to lipopolysaccaride (LPS)-induced lung injury. Old animals demonstrated poor survival and prolonged lung inflammation when compared with young counterparts. At 24 and 72 h after intratracheal LPS administration, expression of the examined factors was down-regulated in the lungs irrespective of age. In conclusion, pulmonary expression of the VEGF family and their receptors declines with age, and is further down-regulated in LPS-induced lung injury, although the mechanism of age- and/or injury-related down-regulation of VEGF remains unknown.