AAV9-mediated VEGF-B gene transfer improves systolic function in progressive left ventricular hypertrophy

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Gene Therapy

Background:

• The transition from compensatory hypertrophy to heart failure is not well understood.
• The specific roles of vascular endothelial growth factors (VEGFs) in this process require further clarification.

Purpose of the Study:

• To investigate the expression profiles of VEGFs and their receptors during the progression of left ventricular hypertrophy (LVH).
• To evaluate the therapeutic potential of adeno-associated virus serotype 9 (AAV9)-VEGF-B(186) gene therapy in preventing heart failure.

Main Methods:

• Left ventricular hypertrophy was induced in C57BL mice using transversal aortic constriction (TAC).
• VEGF and receptor expression was analyzed at multiple time points post-TAC.
• AAV9-VEGF-B(186) gene therapy was administered during the compensatory phase.

Main Results:

• VEGF-C, VEGF-D, and VEGFR-3 were upregulated during compensatory hypertrophy.
• VEGF-B was downregulated in the heart failure stage.
• AAV9-VEGF-B(186) treatment preserved cardiac function by enhancing angiogenesis, inhibiting apoptosis, and promoting cardiomyocyte proliferation.
• Fetal gene expression patterns associated with heart failure were partially reversed by the gene therapy.

Conclusions:

• VEGF-C and VEGF-D are associated with compensatory LVH.
• AAV9-VEGF-B(186) gene transfer can rescue failing heart function and delay the progression to heart failure.