Background: Vascular endothelial growth factor (VEGF) and its receptor may play an important role in the pathogenesis of emphysema. But the effect of another angiogenic factor, placenta growth factor (PlGF), to chronic obstructive pulmonary disease (COPD) is unknown.
Methods: We measured the levels of VEGF and PlGF in serum from patients with COPD (n=184), smokers (n=212), nonsmokers (n=159), and in bronchoalveolar lavage (BAL) fluid from another group (COPD n=20, controls n=18). In vitro cell culture experiments were performed to investigate the effect of PlGF on VEGF.
Results: The serum levels of PlGF were significantly higher in COPD than in controls (27.1 (SE, 7.4) pg/ml vs. 12.3 (SE, 5.1) pg/ml in smokers and 10.8 (SE, 6.3) pg/ml in nonsmokers, p=0.005). The levels of PlGF in BAL fluids were also significantly higher in COPD than in controls (45.7 (SE, 12.3) pg/ml vs. 23.9 (SE, 7.6) pg/ml, p=0.005), associated with an increase of all measured cytokines, like tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8). In COPD patients, the levels of PlGF correlated inversely with forced expiratory volume in one second (FEV1) (in serum, r=-0.59, p=0.002; and in BAL fluids, r=-0.51, p=0.001). While the levels of VEGF in serum were the same between COPD and controls, the levels in BAL fluids were significantly lower in COPD than in controls (127.5 (SE, 30.1) pg/ml vs. 237.8 (SE, 36.1) pg/ml, p=0.002). In cultured bronchial epithelial cells, proinflammatory cytokines induced an increase in the protein expression of both PlGF and VEGF. Continuous concomitant treatment with PlGF, TNF-α and IL-8 stimulation reduced VEGF expression and induced cell death. This phenomenon was suppressed by VEGF receptor inhibitor (CBO-P11).
Conclusions: PlGF was increased in serum and BAL fluids of COPD patients, and correlated inversely with FEV1. Concomitant treatment with PlGF, TNF-α and IL-8 generate detrimental effects on airway epithelial cells. These data suggest that bronchial epithelial cells can express PlGF which may contribute to the pathogenesis of COPD.
- chronic obstruction
- placenta growth factor
- pulmonary disease
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