The vascular endothelial growth factor expression and vascular regeneration in infarcted myocardium by skeletal muscle satellite cells

Background Myocardial infarction results in tissue necrosis, leading to cell loss and ultimately to cardiac failure. Implantation of skeletal muscle satellite cells into the scar area may compensate for the cell loss and provides a new strategy for infarct therapy. Vascular endothelial growth factor （VEGF） is a promising reagent for inducing myocardial angiogenesis. Skeletal myoblast transplantation has been shown to improve cardiac function in chronic heart failure models by regenerating muscle. We hypothesized that VEGF expression and vascular regeneration increased in infarcted myocardium by skeletal muscle satellite cells, which can promote vascular producing and improve survival environment in infarcted myocardium. Methods The skeletal muscle satellite cells were implanted into the infarcted myocardium in a model through ligated left anterior artery in Louis Inbrad Strain rat. Specimens were got for identifying the expression of VEGF and the density of vascular by immunochemical method at two weeks after implantation. Results The proliferation and differentiation of the skeletal muscle satellite cell was very well. The expression of VEGF was higher in the implanted group （146.83±2.49） than that in the control group （134.26±6.84） （P〈0.05）. The vascular density in the implanted group （13,00± 1.51） was also higher than that in the control （10.68 ± 1.79） （P〈0.05）. Conclusion The implanted satellite cell could excrete growth factor that would induce angiogenesis and improve cell survival environment in infarcted myocardium.

Viable Myocardium Impact on Left Ventricular Function after Late Revascularization of Infarct-related Artery in Acute Myocardial Infarction

Objectives The long-term benefit of late reperfusion of infarct-related artery （IRA） after acute myocardial infarction （AMI） is controversial, and the benefit mechanisms remain uncertain. Low dose dobutamine stress echocardiography （LDSE） can identify viable myocardium and predict improvement of wall motion after revascularization. Methods Sixtynine patients with first AMI who did not received early reperfusion therapy were studied by LDSE at 5 to 10 days after AMI. Wall motion abnormality and left ventricular size were measured at the same time. Successful PCI were done in all patients at 10 to 21 days after AMI onset. Patients were divided in two groups based on the presence or absence of viable myocardium. Echocardiography was repeated six months later. Results There were 157 motion abnormality segments. 89 segments （57%） were viable during LDSE. 26 patients （38%） with viability and 43 （62%） without. In viable group, left ventricular ejection fraction （LVEF） was increased （P 〈 0.05）, and left ventricular end systolic volume index （LVESVI） and wall motion score （WMS） were decreased （P 〈 0.05 and P 〈 0.01） significantly at 6 months compared with baseline. But in patients without viability, LVEF was decreased （P 〈 0.01）, and LVESVI and left ventricular end diastolic volume index （LVEDVI） were increased （P 〈 0.05） significantly after 6 months, and the WMS did not changed （P 〉 0.05 ）. LVEF increased （P 〈 0.05 ） and WMS decreased （P 〈 0.05） on LDSE during acute phase in patients with viability, but they were not changed in the nonviable group. Conclusions Late revascularization of IRA in patients with presence of viable myocardium after AMI is associated with long-term preservation left ventricular function and less ventricular remodeling. Improvement of left ventricular systolic function on LDSE indicates late phase recovery of left ventricular function after late revascularization.

Cholesterol metabolic enzyme Ggpps regulates epicardium development and ventricular wall architecture integrity in mice

During embryonic heart development,the progenitor cells in the epicardium would migrate and differentiate into noncardiomyocytes in myocardium and affect the integrity of ventricular wall,but the underlying mechanism has not been well studied.We have found that myocardium geranylgeranyl diphosphate synthase(Ggpps),a metabolic enzyme for cholesterol biosynthesis,is critical for cardiac cytoarchitecture remodelling during heart development.Here,we further reveal that epicardial Ggpps could also regulate ventricular wall architecture integrity.Epicardium-specific deletion of Ggpps before embryonic day 10.5(E10.5)is embryonic lethal,whereas after E13.5 is survival but with defects in the epicardium and ventricular wall structure.Ggpps deficiency in the epicardium enhances the proliferation of epicardial cells and disrupts cell‒cell contact,which makes epicardial cells easier to invade into ventricular wall.Thus,the fibroblast proliferation and coronary formation in myocardium were found enhanced that might disturb the coronary vasculature remodelling and ventricular wall integrity.These processes might be associated with the activation of YAP signalling,whose nuclear distribution is blocked by Ggpps deletion.In conclusion,our findings reveal a potential link between the cholesterol metabolism and heart epicardium and myocardium development in mammals,which might provide a new view of the cause for congenital heart diseases and potential therapeutic target in pathological cardiac conditions.