The effect of rhBMP-2 on pulmonary arterioles remodeling in endotoxin-induced acute lung injury in rats

Endotoxin is known to cause acute lung injury (ALI). Here, we investigated the effects and mechanisms of recombinant human bone morphogenetic protein-2 (rhBMP-2) on pulmonary arteriole remodeling in endotoxin-induced ALI in rats. Sixty Wistar rats were randomly divided into 3 groups (n = 20). Control group was infused with normal saline. Lipopolysaccharides (LPS) alone group was infused with LPS. LPS plus rhBMP2 group was infused with rhBMP-2 and LPS. Lung tissue was harvested. The tunica media of the pulmonary arterioles was measured. The expression levels of survivin, p21, cyclin D1, and activated caspase-3 were examined. The proliferation and apoptosis of pulmonary artery smooth muscle cells were evaluated. The tunica media of pulmonary arterioles in LPS alone group was significantly thicker than both that in control and that in LPS plus rhBMP2 groups (P < 0.01). The multiplication rate in LPS alone group was also significantly higher than both that in control and that in LPS plus rhBMP2 groups (P < 0.01). The apoptotic rate in LPS alone group was lower than that in LPS plus rhBMP2 group (P < 0.01). Compared with the control and LPS plus rhBMP2 groups, the expression levels of mRNA and proteins of survivin and cyclin D1 were increased in LPS alone group (P < 0.01), while the expression levels of p21 and activated caspase-3 were decreased (P < 0.01). RhBMP-2 inhibits the remodeling of pulmonary arterioles in endotoxin-induced ALI, which is achieved by enhancing apoptosis and inhibiting proliferation of pulmonary artery smooth muscle cells.