The Plasma Levels Of IGF-l In Patients With Chronic Cor Pulmonale And Its Significance

Background and objectives Hypoxic pulmonary hypertension (HPH) is the prerequisit for the pax r UOMS of chronic cor pulmonary (CCP), which includes two hnporuinf pathophysiologic changes:hypoxic pulmonary vasoconslnaum and vascular structural remodeling, especially, the latter is tne determinant of the sustained hypoxic pulmonary hypertension. Studies suggest that several kinds of growth factors may be involved n tiic process of vascular structural remodeling. Insulin-like growth la.: (IGF-1) can promote the proliferation and migration of vascular smooth muscle cells and the growth of endothelia cells, incrcs. synthesis of elastin, , and inhibit the cell apoptosis, etc. Studies suggest that hypoxia, abnormal hemodynamic,etc can induce the synthesis and secretion of IGF-1. But, whether the plasma levels of IG1-I change in patients with CCP andwhether there is any relationship between IGF-1 and UPH are not defined. TO elucidate the pathophysiologic significance of IGF-1 in CCP and the relationship between IGF-1 and HPH, we measured plasma IGF-1 levels both in acute exacerbation and remission stages in 30 cases of CCP and analyse its correlation with PaO2 and the ratio of right ventricular pre-ejection period (RVPEP) to the pulmonary flow acceleration time (AT), which reflects the degree of pulmonary hypertension (RVPEP/AT > 1.0 indicating pulmonary hypertension).Subjects and Methods CCP group comprising 30 patients (22 males and 8 females aged 32 to 78; mean + SD age , 61.2+ 12.7 years) was classified into two groups (acute exacerbation and remission stage) according to their clinical presentation. 30 gender-and age-matched healthy subjects served as a normal control group. The plasma levels of IGF-1 were detected by radioimmunoassay. The RVPEP/AT were measured with Doppler echocardiography and PaO2 by arterial b100d gas assay.Results (1) The plasma IGF-1 levels in the acute exacerbation and remission stages of CCP group [(337.84+ 102.22)ng/ml,(284.37 + 99.77)ng/ml] were both higher than those in the normal control group [(231.59+88.99)ng/ml, F<0.01,po.01], and the plasma IGF-1 levels in the acute exacerbation stage were higher than those in the remission stage (po.01). The PaO2 levels in the acute exacerbation stage[(51.53 + 10.98)mmHg] were lower than those in the remission stege [(73.17+ 10.79)mmHg, po.01]. The values of RVPEP/AT in the acute exacerbation stage (1.64+0.30)were higher than those in the remission stage (1.23 + 0.17, po.01). (2) In CCP group, the plasma IGF-1 levels negatively correlated with PaO2 (r=-0.633, po.001; r=-0.828, po.001) and positively correlated with RVPEP/AT (r=0.653, po.001; r=0.470, po.01) in the acute exacerbation and remission stages.Conclusions (1) Plasma levels of IGF-1 both in the acute exacerbation and remission stages in patients with CCP were higher than those in the normal control group,especially in the former stage; In CCP group, plasma IGF-1 levels positively correlated with RVPEP/AT and negatively correlated with PaO both in the acute exacerbation and remission stages. These findings suggests that IGF-1 involves in pathophysiology of CCP. (2) The increase in plasma levels of IGF-1 is in accordance with the increase in the pulmonary arterial pressure and the decrease in PaO2, which indicate that the increased synthesis and secretion of IGF-1 stimulated by hypoxia and pulmonary hypertension may contribute to the augmented IGF-1 levels. (3) It can be speculated that IGF-1 participates in the occurrence and development of HPH. Inhibiting its biological activity by IGF-IT antagonist or blocking its local synthesis and secretion by an sense IGF-1 gene technology may become a new therapy for HPH.