Changes And Significance Of Serum Vegf And Tgf-β ₁ In The Children Of Congential Heart Disease With Pulmonary Hypertension

Objective:About ten to fifteen thousand congential heart disease babies born every year in our country, and 50% of them suffer from left-to-right shunt congential heart disease. Large left-to-right shunt from the defect leads to high pulmonary blood flow which is the major feature of pathology and physiology in the disease. Pulmonary hypertension is a disease that possesses the major feature of pulmonary arteriole vasospasm, endomembrance accrementition and reconstitution, pulmonary arteriole vascular proliferation and reconstitution leads to pulmonary vascular resistance accrescencing progressively and eventually causes cardia failure and death. Pulmonary hypertension induces by high pulmonary blood flow is the most serious and common complication of the left-to-right shunt congential heart disease, which degree will directly affect operating result and prognosis. Up to now, it is not completely clear about the pathogenesis of the pulmonary hpertention. Studies suggest that the major pathology and physiology changes of pulmonary hypertension is vascular endothelial cell damage, accrementition and functional disturbance ,then leads to pulmonary vascular remodeling, that plays a very important part in the genesis and development of pulmonary hpertention. Many growth factors participate in this process, among them vascular endothelial growth factor which could specificly promote vessel endothelium division, proliferation and immigration,which is recognized as the central modulator of angiogenesis,is the most important angiogenesis factor. However, more and more evidence indicate that a specific cell factor stimulates cellular reaction is not isolate, but depends on the existence other regulatory factors. Also vascular endothelial growth factor is no exception, which expression is influenced by many factors such as transforming growth factor-β1. Transforming growth factor-β1 is an effective regulator of cellular proliferation and differentiation. Brogi had discovered that TGF-β1 could up-regulate expression of VEGF to promote growth of blood vessel. From now on, it is clear that the effectiveness of VEGF in the reconstitution of pulmonary vascular structure about pulmonary hypertension, although there are many studys on the effectiveness of TGF-β1 on animal experiments but few on clinic experiment about pulmonary hypertension of patients with congenital heart disease in world. Moreover there is no research on the interaction between VEGE and TGF-β1 about congenital heart disease with pulmonary hypertension. This dissertation, by detecting content of serum vascular endothelial growth factor and transforming growth factor-β1 in the peripheral vein of patients with left-to-right shunt congential heart disease complicated with pulmonary hypertension, is designed to identify the association of VEGF and TGF-β1 with the occurrence and development of pulmonary hypertension, as well as the correlation between the two factors, then to explore the effect and clinical significance of them on children with CHD compicated with pulmonary hupertention.Methods: Fouty-two patients with left-to-right shunt congential heart disease were selected from cardiac surgery in The Fourth Hospital of Hebei Medical University and The Fist Hospital of Hebei Medical University who were divided to three groups according to pulmonary artery systolic pressure (PASP) by Doppler echocardiography before operation:group one was not pulmonary hypertention (PASP < 30mmHg , n=12),group two was mild pulmonary hypertention (PASP30~49mmHg,n=12),group three was heavy pulmonary hypertention (PASP≥50mmHg,n=12). All patients of CHD were collected blood of peripheral vein before extracorporeal circulation operation, and then obtained serum. Serum vascular endothelial growth factor and transforming growth factor-β1 were ditected by enzyme-linked immunosorbent assay (ELISA). To record age, weight, height and PASP of all selected patients. Combined with comparative analysis of relevant clinical data, a statistical treatment was conducted. Results:1 The change of serum VEGF levels of patients with congential heart disease in three groupsSerum VEGF level of not pulmonary hypertention group was lower than mild pulmonary hypertention group, there was a statistically difference (P<0.05).Serum VEGF level of not pulmonary hypertention and mild pulmonary hypertention group were significantly lower than heavy pulmonary hypertention group , there was a obvious statistically difference (P<0.01).2 The change of serum TGF-β1 levels of patients with congential heart disease in three groupsSerum TGF-β1 level of not pulmonary hypertention group was lower than mild pulmonary hypertention group, there was a statistically difference (P<0.05).Serum TGF-β1 level of not pulmonary hypertention and mild pulmonary hypertention group were significantly lower than heavy pulmonary hypertention group , there was a obvious statistically difference (P<0.01).3 The correlation analysis3.1 The correlation analysis of serum VEGF and PASPIn not pulmonary hypertention group, serum VEGF and PASP was of no obvious Correlation, there was no statistically difference(r=0.383,P>0.05).in mild pulmonary hypertention group, serum VEGF and PASP was of Correlation, there was statistically difference(r=0.648,P<0.05).in heavy pulmonary hypertention group, serum VEGF and PASP was of Correlation, there was statistically difference(r=0.618,P<0.05).42 patiens'serum VEGF and PASP was of significant correlation, there was obvious statistically difference(r=0.876,P<0.01).3.2 The correlation analysis of serum TGF-β1 and PASPIn not pulmonary hypertention group, serum TGF-β1 and PASP was of no obvious Correlation, there was no statistically difference(r=-0.238,P>0.05).in mild pulmonary hypertention group, serum TGF-β1 and PASP was of Correlation, there was statistically difference(r=0.573,P<0.05).in heavy pulmonary hypertention group, serum TGF-β1 and PASP is of Correlation, there is statistically difference(r=0.677,P<0.05).42 patiens'serum TGF-β1 and PASP was of significant correlation, there was obvious statistically difference(r=0.888,P<0.01).3.3 The correlation analysis of serum VEGF andTGF-β1serum TGF-β1 and PASP was of significant correlation, there was obvious statistically difference(r=0.888,P<0.01).Conclusion:1 The level of serum VEGF increases obviously when patients suffer from congential heart disease with pulmonary hypertension, the change of which is coincide with the degree of pulmonary hypertension, which suggests that VEGF participates in the formation of PH, meanwhile indicates that it can reflect the degree of PH.2 The level of serum TGF-β1 increases obviously when patients suffer from congential heart disease with pulmonary hypertension, the change of which is coincide with the degree of pulmonary hypertension, which shows that TGF-β1 play a role in the formation of PH, meanwhile impots that it can reflect the degree of PH.3 There is obvious positive correlation of VEGF and TGF-β1 when Patients suffer from congential heart disease with pulmonary hypertension.TGF-β1 is the upstream element of VEGF, which can induce the expression of VEGF to accommodate the generation of blood vessel, that play an important part in the formation of PH.4 VEGF and TGF-β1 can be as laboratory indicators for monitoring the changing process of the occurrence and development of pulmonary hypertension, as well as for observing surgical treatment, which is certain meaning and clinic value.5 By researching VEGF and TGF-β1 deeply, applicating molecular biology technogy to develop VEGF,TGF-β1 and its receptor monoclonal antibody or gene therapy for early prevention and treatment of pulmonary hypertension to expand new ways.