Direct Pro-Inflammatory Effect of C-Reactive Protein on Human Pulmonary Artery Endothelial Cells

Abstract

C-reactive protein (CRP) has a prognostic role in cardiovascular and pulmonary diseases. Recent data suggest its pro-inflammatory effects in atherosclerotic lesion formation. This raises the hypothesis of whether or not CRP has pro-inflammatory effects on pulmonary vasculature by inducing the production of endothelin-l (ET)-l, a potent vasoconstrictor and proliferative cytokine, and expression of adhesion molecules which could culminate in inflammatory cell recruitment and vascular injury. Human pulmonary artery endothelial cells (HPAECs) were cultured and incubated with 25ptg/ml of human recombinant CRP and with interleukin (IL)-lP 10ng/ml, a well-known activator of endothelial cells, which served as a positive control for 24 hours. Expression of vascular cell adhesion molecule (VCAM)-l and intercellular adhesion molecule (ICAM)-l was assessed by flow cytometry. Secretion of ET-l from HPAECs was also evaluated. In this study we show that incubation of HPAECs with human recombinant CRP for 24 hours induced a significant increase in ICAM-l expression (from 610 to 6553 mean fluorescence intensity, p < 0.005) and VCAM-l expression (from 212 to 303 mean fluorescence intensity, p < 0.05), as compared to control. Adhesion molecule induction was similar to that observed in endothelial cells activated with IL-lp. Likewise, CRP potentiated the ET-l production by HPAECs. The levels of ET-l were significantly higher at 24 hours (controI19.94±3 vs CRP 46.54±18 pg/ml, p < 0.05). In conclusion, this study makes a novel observation that CRP induces expression of adhesion molecules and secretion of ET-l in HPAECs. Our study provides the first evidence that CRP exerts direct proinflammatory effects on pulmonary artery endothelial cells.Pulmonary arterial hypertension (PAH) is a severe disease ofthe small pulmonary arteries characterized by vascular narrowing and raised pulmonary artery pressure leading to the development of right-sided