Renal Therapeutic Angiogenesis Using a Bioengineered Polymer-Stabilized Vascular Endothelial Growth Factor Construct

Area of Science:

• Nephrology
• Vascular Biology
• Biotechnology

Background:

• Renovascular disease (RVD) causes microvascular rarefaction, leading to progressive kidney injury.
• Previous vascular endothelial growth factor (VEGF) therapies showed limited efficacy at clinical doses due to bioavailability issues.
• A novel biopolymer-stabilized elastin-like polypeptide (ELP)-VEGF fusion protein was developed to enhance VEGF bioavailability.

Purpose of the Study:

• To evaluate the in vivo therapeutic potential of ELP-VEGF for renal angiogenesis in a swine model of chronic RVD.
• To assess the impact of ELP-VEGF on renal microvascular density, fibrogenic activity, and overall kidney function.

Main Methods:

• Chronic RVD was induced in swine, followed by single-kidney infusion of ELP-VEGF, unconjugated VEGF, ELP alone, or placebo.
• Renal blood flow (RBF) and glomerular filtration rate (GFR) were measured.
• Protein expression of VEGF, Flk-1, and downstream angiogenic mediators was analyzed.
• Microvascular density and fibrogenic markers were assessed post-treatment.

Main Results:

• ELP-VEGF demonstrated high renal binding after infusion.
• Therapy with ELP-VEGF restored renal protein expression of VEGF, Flk-1, and angiogenic mediators.
• Restored microvascular density and attenuated fibrogenic activity were observed.
• Significant improvements in RBF and GFR were achieved with ELP-VEGF compared to controls.

Conclusions:

• ELP-VEGF therapy is a feasible approach to curtail renal injury in RVD.
• The therapy enhances renal angiogenic signaling and reduces fibrogenic activity, ameliorating microvascular rarefaction.
• This novel fusion protein holds promise for improving renal function and treating progressive kidney disease.