🧬 Can muscle hypertrophy be improved by building the vasculature first? A new preprint explores a clever sequential gene-therapy strategy: VEGF-A165 plasmid → AAV9-follistatin (FST344) to couple angiogenesis with muscle growth. In C57BL/6 mice, the combination produced: 🔹 Greater muscle hypertrophy — R/L muscle mass ratio 1.176 vs 1.113 with AAV-FST alone; combination p=0.004, Cohen’s d=2.04. 🔹 ~2× higher CD31⁺ vessel density, while simultaneously producing the largest muscle fibres. 🔹 ~2.1× higher muscle FST mRNA than AAV-FST alone at Day 115. 🔹 A 2.6× higher muscle-to-liver transgene expression ratio, suggesting that angiogenic preconditioning may improve local AAV targeting/transduction. The biology is compelling: anabolism without adequate capillarization may produce bigger muscle, but not necessarily better muscle. VEGF preconditioning could help coordinate fibre growth with vascular adaptation—a potentially important concept for sarcopenia, cachexia, and neuromuscular disease. Important caveat: this is a small mouse study and muscle strength/function was not measured, so whether the added mass translates into functional benefit remains unknown. 📄 Sequential VEGF-A165 plasmid and AAV-follistatin gene therapy enhances muscle hypertrophy and capillarisation in C57BL/6 mice 🔗 DOI: 10.64898/2026.08.26.747237 #Sarcopenia #Muscle #GeneTherapy #Follistatin #VEGF #AAV #Angiogenesis #Cachexia #Aging #RegenerativeMedicine