Aims To investigate the effect and mechanism of HIF-1a on rat AMI therapy by MSC transplantation. Materials and methods Rat acute myocardial infarction model is made through coronary anterior descending artery ligation. Rats are randomly divided into four groups which are sham operation group, pure infarction group, infarction & MSC transplantation group and infarction & HIF-1a transfected MSC transplantation group. Eight rats from every group are observed. The cell transplantation is carried out immediately after the acute myocardial infarction model is successfully made. The rats are put to death 4 weeks after the operation and the heart is isolated for weight measuring, heart chamber and myocardium thickness testing. We also observe the myocardial angiogenesis in and around the infarct myocardium through HE staining, and the distribution of transplanted cells in the myocardium tissue under immunofluorescence staining. Western blot and RT-PCR is used to test the expression of HIF-1a and VEGF in the myocardium.
Results About 37% of the operations on AMI model making are successful. More MSCs transfected with HIF-1 are alive after transplantation than other groups (p<0.05). Heart weight and left ventricular chamber of the rats transplanted with MSCs transfected with HIF-1a are lower and smaller than the other three groups (p<0.05), the thickness of the left ventricular well is much thicker than the others (p<0.05). Capillary regeneration in and around the infarction area is greater than the others (p<0.05). Higher expression of HIF-1a (p<0.05) and VEGF (p<0.05) can be detected in the myocardium of the arts transplanted with MSCs transfected with HIF-1a.
Conclusions HIF-1a could raise the survival rate of MSC in the infarct myocardium area. MSC transfected with HIF-1a could restrain myocardium remodelling after infarction, and raise the density of capillary around infarction, which might be the mechanism of the former.