Targeting endothelial metabolism for anti-angiogenesis therapy: A pharmacological perspective

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Current anti-angiogenic therapies targeting growth factor signaling show limited success due to resistance.
• Endothelial cells (ECs) are crucial for pathological angiogenesis in malignant and ocular diseases.
• Emerging evidence highlights the convergence of growth factor signaling onto cellular metabolism in ECs.

Purpose of the Study:

• To explore novel anti-angiogenic therapies by targeting cellular metabolism in ECs.
• To investigate the role of glycolysis and fatty acid β-oxidation (FAO) in EC proliferation and migration.
• To provide proof-of-concept for pharmacological inhibition of metabolic pathways to control angiogenesis.

Main Methods:

• Review of recent studies on EC metabolism and angiogenesis.
• Analysis of the role of glycolysis and FAO in ECs.
• In vivo validation of pharmacological inhibitors of metabolic pathways.

Main Results:

• ECs utilize glycolysis for energy and biomass, essential for proliferation and migration.
• Fatty acid β-oxidation (FAO) is critical for nucleotide synthesis during EC proliferation.
• Pharmacological inhibition of these metabolic pathways demonstrated efficacy in inhibiting pathological angiogenesis in vivo.

Conclusions:

• Targeting EC metabolism represents a promising alternative strategy for anti-angiogenic therapy.
• Further research is needed to explore other metabolic pathways and their therapeutic potential.
• Inhibiting glycolysis and FAO in ECs can effectively reduce pathological angiogenesis.