Table 3 Potential therapeutic strategies targeting AGEs in cardiovascular disease
Therapeutic strategy | Specific targets/compounds | Mechanism of action | Preclinical/clinical studies | Limitations/challenges |
|---|---|---|---|---|
Inhibiting AGE formation and accumulation | Aminoguanidine, Pyridoxamine | Blocking the formation of AGEs by trapping reactive carbonyl species | Preclinical, limited clinical trials | Side effects, limited efficacy |
| Â | Alagebrium (ALT-711) | Breaks AGE crosslinks, reduces AGE accumulation | Preclinical, Phase II clinical trials | Safety concerns, Incomplete efficacy |
Blocking AGE-receptor interactions | Soluble RAGE, Anti-RAGE antibodies | Competitively inhibits binding of AGEs to RAGE, preventing receptor activation | Preclinical, Phase I clinical trials | Limited efficacy, Immunogenicity |
| Â | AGER1/OST-48 overexpression | Enhances AGER1-mediated suppression of RAGE signaling | Preclinical | Challenges in gene therapy delivery |
Targeting downstream signaling pathways | Inhibition of NF-κB, MAPK, PI3K/Akt | Reduces AGE-induced pro-inflammatory responses and oxidative stress | Preclinical | Potential off-target effects |
| Â | Inhibition of NADPH oxidase | Reduces AGE-induced reactive oxygen species (ROS) production | Preclinical | Potential off-target effects |
Antioxidant and anti-inflammatory therapies | N-Acetylcysteine, Vitamin E, Curcumin | Scavenges free radicals and reduces inflammation, indirectly targeting AGE pathways | Preclinical, Some clinical studies | Limited efficacy, Need for specificity |