| Background and objectives Hypoxic pulmonary hypertension (HPH) is the prerequisite for the pathogenesis of chroinc cor pulmonale (CCP), which includes two important pathophysiologic changes: hypoxic pulmonary vasoconstriction and 昿ulmonary vascular remodelling, especially the latter is the determinant of the sustained HPH. Studies suggest that many active material and several growth factors may be invovlved in process of vascular structural remodeling, Matirx metalloproteinase-1 (MMP-1) and epidermal growth factor (EGF) are the two of them. The matirx metalloproteinases are a family of proteinase with zinc ion acting as assistant factor, the MMP-1 controls deposition and degradation of extracelluar matrix(ECM), and facilitate proliferation and migration of vascular smooth muscle cells (VSMC). Studies suggest that the activation of MMP-1 may trigger the formation of HPH. The EGF can promote the proliferation and migration of VSMC and proliferation of endothelial cell, stimulates adventitial fibroblast to proliferate and differentiate, also stimulates the production ECM, but inhibits degradation of ECM. But the serum levels of MMP-1 and EGF in patients with CCP remains unreported. To elucidate the relationship between MMP-1 and EGF and their pathophysiologic role and significance in HPH, we measured serum levels both in acute exaceration and remission stages in 30 cases of CCP and analyse its correlation with Pa02 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 indicting pulmonaryhypertension).. ?Subject and Method CCP group comprising 30 patients (18 males and 12 femalesaged 48 to 77 years;mean SD age, 66 + 8. 9 years) was classified into two groups (acute exaceration and remission stages)according to their clinical presentation. 30 gender-and age-matched healthy subjects served as a normal control group.the serum levels of MMP-1 and EGF were detected by enzyme linked immunosorbent assay(ELISA^. The RVPEP/AT ratios were measured with Doppler echocardiography and the Pa02 levels by arterial blood gas assay.Results(1)lhe serum MMP-1 levels in the acute exaceration and remission stages of CCP group [ (120. 88 14. 88) ng/ml, (92. 87 13. 71) ng/ml] were both higher than that in the normal control group[(60. 98 + 12. 24)ng/ml, P<0. 001, P<0. 001], and the serum MMP-1 level in the acute exaceration stage was higher than that in the remission stage (p<0. 001). (2) The serum EGF levels in the acute exaceration and remission stages of CCP group [(593.84 38. 04)pg/ml, (416. 29 + 29. 75) pg/ml] were both higher than that in the normal control group [(242. 14 + 27. 29)pg/ml, P<0. 001, P<0. 001], and the serum EGF level in the acute exaceration stage was higher than that in the remission stage(p<0. 001). (3) The PaO2 level in the acute exaceration stage[(52. 77 5. 23)mmHg] was lower than that in the remission stage [(74. 84 + 4. 49)mmHg, P<0. 001]. The ratio of RVPEP/AT in the acute exaceration stage (1.51 0. 10) was higher than that in the . remission stage[(1. 28 0. 09), P<0. 001], and the mean ratios of RVPEP/AT in the two stages were more than one. (4) In CCP group, the serum MMP-1 levels were negatively correlation with PaOz(r=-0. 81, P<0. 001;r=-0. 73, P<0. 001) and positively correlation with RVPEP/AT(r=0. 78, P<0. 001 ;r=0. 72, P<0. 001) in the acute exaceration and remission stages. (5) In CCP group, the serum EGF levels were negatively correlation with Pa02 (r=-0. 76, P<0.001;r=-0.74, P<0.001) and positively correlation with RVPEP/AT (r=0. 77,P<0.001:r=0. 62, P<0.001) and positively correlation with the serum MMP-1 levels (r=0. 87, P<0. 001;r=0. 84, P<0. 001 ) in the acute exaceration and remission stages.Conclusion (1) The serum MMP-1 levels in the acute exaceration and remission stages in patients with CCP group were both higher than that in the normal control group, especially in the for... |
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