The Serum Levels And Significance Of TGF-β1,MMP-2 In Patients With Chronic Cor Pulmonale

Background and objectives Hypoxic pulmonary hypertension (HPH) is theprerequisite for the pathogenesis of chronic cor pulmonale (CCP), but its mechanisms are not very clear. Hypoxic pulmonary vasoconstriction and pulmonary vascular remodeling play important roles in the pathogenesis of HPH, especially, the latter is the determinant of the sustained hypoxic pulmonary hypertension, and restricted the effect of vasodilator applied in clinical practice. Transforming growth-factor betal (TGF- β₁)can promote the proliferation and migration of vascular smooth muscle cells and proliferation of endothelial cell, stimulates adventitial fibroblast to proliferate and differentiate, also stimulates the production of extracellular matrix components, but inhibits degradation of ECM. The matrix metalloproteinase (MMPs) are a family of proteinase with zinc ion acting as assistant factor, the distribution of MMP-2 is the most prevailing in all MMPs. MMPs control ECM deposition and degradation, they facilitate proliferation and migration of vascular smooth muscle cells (SMC). Studies suggest that the activation of MMPs may trigger the formation of HPH. But the serum levels of TGF- β₁ and MMP-2 in patients with CCP remains unreported, the relationship between TGF- β₁ and MMP-2 is not defined. To elucidate the relationship between TGF- β₁ and MMP-2 and their pathophysiologic role and significance in HPH, we measured serum levels both in acute exacerbation and remission stages in 28 cases of CCP and analyse its correlation with PaO₂ and the ratio of right ventricular pre-ejection period (REPEP) to the pulmonary flow acceleration time (AT), which reflects the degree of pulmonary hypertension(RVPEP/AT>1.0 indicating pulmonary hypertension).Subject and Method CCP group comprising 28 patients (21 males and 7 females aged 46 to 76 years; mean?SDage, 65 + 8.4years) was classified into two groups (acute exacerbation and remission stage ) according to their clinical presentation. 28 gender-and age-matched healthy subjects served as a normal control group. The serum levels of TGF β₁ MMP2 were detected by enzyme linked immunosorbent assay (ELISA). The RVPEP/AT values were measured with Doppler echocardiography and the PaO₂ levels by arterial blood gas assay.Results (1) The serum TGF β₁ levels in the acute exacerbation and remission stages ofCCP group [(13.53?.16)ng/ml, (7.97+1.5l)ng/ml] were both higher than those in the normal control group [(4.30+ 1.42)ng/ml, P<0.001,P<0.001], and the serum TGF β₁ levels in the acute exacerbation stage was higher than those in the remission stage (P<0.001). (2) The serum MMP-2 levels in the acute exacerbation and remission stages of CCP group [(401.75 + 43.86)ng/ml, (347.39+36.23)ng/ml] were both higher than those in the normal control group [(271.73 ?37.3)ng/ml,P<0.001 P<0.001],and the serum MMP-2 levels in the acute exacerbation stage was higher than those in the remission stage (P<0.001). (3) The PaO₂ levels in the acute exacerbation stage [(53.31 +6.03 )mmHg] were lower than those in the remission stage[(77.41+5.35) mmHg, P<0.001], The value of RVPEP/AT in the acute exacerbation stage (1.53+0.11) were higher than those in the remission stage (1.26+0.10, P<0.001), and the mean values of RVPEP/AT hi the two stages were more than one. (4) In CCP group, the serum TGF β₁i levels negatively correlated with PaO2 (r=-0.80,P<0.001; r=-0.77,P<0.001) and positively correlated with RVPEP/AT (r=0.89,P<0.001; T=.076,P<0.001) in the acute exacerbation and remission stages. (5) In CCP group, the serum MMP-2 levels negatively correlated with PaO2 (r=-0.82,P<0.001; r=-0.65,P<0.001) and positively correlated with RVPEP/AT(r=0.70 P<0.001; r=0.75 P<0.004) and positively correlated with the serum TGF β₁ levels in the acute exacerbation and remission stages.Conclusions (l)The serum TGF β₁ levels in the acute exacerbation and remission stages in patients with CCP group were both higher than those in the normal control group,esp...