The experimental study of andrographolide attenuating hypoxia-induced pulmonary hypertension in a mouse model

Abstract

Chronic hypoxia induces pulmonary arterial hypertension (PAH). Smooth muscle cell (SMC) proliferation and hypertrophy are important contributors to the remodeling that occursin chronic hypoxic pulmonary vasculature. The NF-κB transcription factors modulate the expression of tissue factor (TF), E-selectin (CD62E) and vascular cell adhesion molecule-1 (VCAM-1), which are essential for the arterial remodeling. andrographolide (Andro) covalently modifies the reduced cysteine62 of p50-am ajor subunit of NF-κB transcription factors, thus blocking the binding of NF-κB transcription factors to the promoters of their target genes, preventing NF-κB activation and inhibiting inflammation in vitro and in vivo. Here we report that Andro,but not its inactive structural analog 4H-Andro, significantly suppressed hypoxia-induced pulmonary hypertension in a murine model. Consistently, p50-/- mice manifested attenuated the same results. Our data thus indicate that, by the inhibition of the NF-κB that are important in thrombosis and inflammation,specific inhibitors of p50, such as Andro, may be therapeutically valuable for preventing and treating hypoxia-induced pulmonary hypertension. Key words: NF-κB transcription factors; andrographolide; Hypoxia-induced pulmonary hypertension; Tissue factor