The Influence Of VEGF On Regulating Sarcoplasmic Reticulum Calcium Pump Activity And Protecting Myocardial Infarction

Objectives:VEGF-A is the most characteristic one of VEGF family members, and its function is the strongest. VEGF-A has been shown to have anti-apoptotic role and can maintain stability and neovascularization in neonatal cardiac myocytes. VEGF-A is divided into five subtypes, of which VEGF165 is the most representative and most important isomer. VEGF165 mainly regulate the expression of its receptor VEGFR2, thereby improving the reconstruction of muscle fibers, VEGF exerts its biological effects mainly by binding to VEGFR2 after AMI.VEGF and VEGFR2 combining activates phospholipase C(phospholipase C, PLC), which led to inositol triphosphate(inositol 1,4,5-triphosphate, IP3) formation, IP3 caused intracellular Ca2+ increases.Sarcoplasmic reticulum SERCA2 a can pumpe back Ca2+ in the sarcoplasmic reticulum, regulate intracellular free Ca2+ concentration, influence relaxation and contraction of myocardial cells. SERCA2 a activity was adjusted by Ca2+ concentration within cytosolic. The higher the concentration of free Ca2+ in the cytoplasm, the SERCA2 a activity higher. And its combining with storage proteins and storage, is a self-regulating mechanism. So, we guess there is some inevitable linking between VEGF and SERCA2, which is likely associated with Ca2+.To test this conjecture, we examined the effects of VEGF on SERCA2 a activity and its mechanism.Materials and Methods: Adenovirus was amplified, purified and titer measured, and prepared for the follow-up test. The 6-week-old ICR mice were randomly divided into sham group, Ad-VEGF group, Ad-GFP group, SU5416 group, and then ligated the front descending coronary artery and built mouse model of myocardial infarction and myocardial were injected Ad-VEGF, Ad-GFP, SU5416(VEGFR2 inhibitor).Into myocardial infarction bord area, confirmed by ECG changes, Then ECG detecting to confirm myocardial infarction model was successful or not; Echocardiography test to look into heart function in mice; measuring mouse right hind tibia length; ELISA was used to detect serum levels of Tn-I; Use colorimetry to test SERCA2 a activity. Western blot was used to detect VEGF, PLN, P-T17 PLN, P-S16 PLN, SERCA2 a, HAX 1-expression in the myocardial tissue. HE and Masson staining to see myocardial tissue condition. Tunnel measured heart tissue apoptosis.Results: MI model was successful. VEGF can improve heart function and SERCA2 a activity after myocardial infarction, were reduced after blocking VEGF receptor. Tn-I test showed that VEGF decrease myocardial injury and increase myocardial regeneration., showed enhanced SERCA2 a activity and reduced myocardial remodeling and apoptosis.Conclusions: VEGF can enhance the cardiac sarcoplasmic reticulum calcium pump activity, improve heart function after myocardial infarction and has a protective effect on myocardial infarction.