Abstract
Pulmonary arterial hypertension (PAH) is a fatal disease characterised by increased pulmonary vascular resistance and abnormal pulmonary arteriolar remodelling, mainly due to pulmonary artery smooth muscle cell (PA-SMC) hyperplasia. Insulin-like growth factor-1 (IGF-1), a mitogen for vascular SMCs, has been implicated in the pathogenesis of atherosclerosis. Moreover, low circulating IGF-1 levels are associated with an increased risk for cardiovascular diseases.
We, therefore, hypothesized that the IGF-1 signaling could play a role in PAH pathogenesis.
Relative gene expressions of IGF-1 and IGF-1 receptor were evaluated in total lung homogenates and in cultured PA-SMCs from PAH patients (n=6) and controls (n=10). PA-SMCs treated with IGF-1 (10 and 100ng/mL) were assessed for cell proliferation (by MTT assay and cell counting) and apoptosis (by Bax/Bcl-2 evaluation). Seric IGF-1 levels were evaluated by ELISA in sera from PAH patients (n=25) and controls (n=26).
Expression of IGF-1 was 5-fold increased in total lung homogenates from PAH patients compared to controls, while pulmonary IGF-1 receptor expression did not change. In PA-SMCs from PAH patients, the expressions of IGF-1 and IGF-1 receptor were increased. Treatment with IGF-1 dose-dependently induced proliferation and decreased Bax/Bcl-2 ratio in PA-SMCs. These effects were stronger in PA-SMCs from PAH patients compared to controls. After adjustment for age and body mas index, seric IGF-1 level was higher in PAH patients compared to controls.
In PAH patient, the paracrine IGF-1 signalling is exacerbated in the lungs, probably contributing to PA-SMC hyperplasia, while circulating IGF-1 is reduced.
- © 2014 ERS