Vascular Endothelial Growth Factor For Aortic Stenosis Leading To Study The Protective Effects Of Heart Failure

Aortic stenosis is one of the most common cardiac valve diseases with a prevalenceof2-7%above the age of65years old. Surgery with aortic valve replacement forsevere symptomatic aortic stenosis is currently the only treatment option, resulting ina5-year survival rate of60-70%. Unfortunately, in patients with poor ventricularfunction, the mortality and long-term outcome is unsatisfied, and only a minority ofthese patients can undergo surgery.The principal aim of this thesis is to better understand the molecular mechanisms bywhich aortic stenosis induced heart failure. Furthermore, we explore possibleapproaches to prevent the heart injury, improve the postoperative recovery anddecrease the mortality of the patients.Objective: We hypothesize that pre-operative treatment with VEGF will improve theaortic stenosis patients’ condition, to be better suitable for aortic valve replacement.In the present study, we tested this hypothesis in mice model with ligature-inducedaortic stenosis (AS).Methods: Adult male mice were subjected to either AS or sham surgery. Two weekslater, adenoviral VEGF (Ad-VEGF), enhanced green fluorescence protein (Ad-EGFP,as a parallel control) or saline was injected into left ventricle free wall of AS mice.Two weeks after delivery, all mice were measured by echocardiography and harvestedfor further detection.Results: AS for four weeks caused cardiac hypertrophy and left ventriculardysfunction. VEGF treatment increased capillary density, protected mitochondrialfunction, reduced CMs apoptosis, promoted CMs proliferation and eventuallypreserved cardiac function. Conclusion: Our findings indicate that VEGF could repair AS-induced transitionfrom compensatory cardiac hypertrophy to heart failure.