Gangrene, revascularization, and limb function improved with E-selectin/adeno-associated virus gene therapy

Area of Science:

• Vascular Biology
• Regenerative Medicine
• Gene Therapy

Background:

• Critical limb ischemia (CLI) necessitates novel therapeutic strategies for limb salvage.
• E-selectin, a cell-adhesion molecule, plays a crucial role in recruiting stem/progenitor cells for neovascularization in ischemic tissues.

Purpose of the Study:

• To investigate the efficacy of E-selectin/adeno-associated virus (AAV) gene therapy in promoting therapeutic angiogenesis and improving outcomes in a murine model of hindlimb ischemia and gangrene.

Main Methods:

• Mice with induced hindlimb ischemia and gangrene received intramuscular injections of either E-selectin/AAV or LacZ/AAV.
• Gangrene severity was assessed using the Faber score.
• Reperfusion, angiogenesis, and hindlimb functionality were evaluated using laser Doppler perfusion imaging, microscopy, and treadmill tests, respectively.

Main Results:

• E-selectin/AAV treatment significantly reduced gangrene scores and increased capillary density in ischemic footpads compared to controls.
• Improved hindlimb reperfusion and enhanced exercise tolerance were observed in the E-selectin/AAV group.
• The gene therapy also led to lower relative muscular atrophy.

Conclusions:

• E-selectin/AAV gene therapy effectively promotes hindlimb angiogenesis, reperfusion, and functional recovery in a murine model of critical limb ischemia and gangrene.
• This novel gene therapy approach represents a potential therapeutic strategy for future clinical investigations in CLI patients.