Gene therapy targeting inflammation in atherosclerosis

Area of Science:

• Cardiovascular Research
• Immunology
• Molecular Biology

Background:

• Atherosclerosis involves immune cell infiltration into the vascular wall, a process influenced by reactive oxygen species (ROS).
• ROS contribute to LDL oxidation, foam cell formation, and activation of redox-sensitive transcription factors (e.g., NF-kappa B, AP-1), regulating inflammatory genes in atherogenesis.

Purpose of the Study:

• To explore the potential of gene delivery strategies in combating atherosclerosis.
• To review the efficacy of delivering genes encoding antioxidant enzymes, eNOS, or regulators of redox-sensitive transcription factors in preclinical models.

Main Methods:

• Gene delivery of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, heme oxygenase-1).
• Gene delivery of endothelial nitric oxide synthase (eNOS).
• Gene delivery of ROS scavengers and regulators of transcription factors (NF-kappa B, AP-1, Nrf2).

Main Results:

• Gene delivery strategies successfully suppressed atherogenesis in animal models.
• Delivery of antioxidant enzymes, eNOS, and ROS scavengers demonstrated therapeutic effects in experimental studies.

Conclusions:

• Gene delivery techniques offer novel approaches for cardiovascular research in atherosclerosis.
• Clinical translation is hindered by challenges with gene vectors, immune responses, side effects, and achieving sustained local gene expression, making clinical gene therapy for atherosclerosis premature.