Respiratory Research volume 18 , Article number: Cite this article. Metrics details. Tobacco-induced pulmonary vascular disease is partly driven by endothelial dysfunction. The Sonic hedgehog SHH pathway is involved in vascular physiology. We sought to establish whether the SHH pathway has a role in pulmonary endothelial dysfunction in smokers. The ex vivo endothelium-dependent relaxation of pulmonary artery rings in response to acetylcholine Ach was compared in 34 current or ex-smokers and 8 never-smokers.
The results were expressed as a percentage of the contraction with phenylephrine. SHH pathway gene expression was quantified in reverse transcriptaseβquantitative polymerase chain reactions. All SHH pathway genes were expressed in pulmonary artery rings from smokers. VEGF gene and protein expression levels in the pulmonary artery rings were positively correlated with the degree of Ach-induced relaxation and negatively correlated with the number of pack-years.
SHH pathway genes and proteins are expressed in pulmonary artery rings from smokers, where they modulate endothelial function through VEGF. Pulmonary vascular remodelling can occur in smokers, regardless of whether the latter have normal or impaired lung function [ 1 ]. These vascular changes may ultimately lead to increased pulmonary vascular resistance and subsequent pulmonary hypertension, which is a negative prognostic factor.
Pulmonary endothelial dysfunction is thought to be an early pathophysiological determinant of this vascular remodelling. Endothelial dysfunction has been reported in patients with end-stage chronic obstructive pulmonary disease COPD [ 2 ], patients with mild COPD, and smokers with normal lung function [ 3 ].
Sonic hedgehog SHH is a developmental pathway that controls epithelial-mesenchymal interactions during the morphogenesis of various organs including the lungs and also influences lung branching [ 4 ]. The SHH pathway also plays a key role in cell differentiation and proliferation [ 5 ], and in tissue repair after ischaemia [ 6 ].
