In the battle against thrombosis, a silent killer responsible for millions of deaths worldwide, scientists have long sought effective strategies to prevent blood clots. Now, a groundbreaking study led by Weiliang Deng from the State Key Laboratory of Medicinal Chemical Biology at Nankai University in China, has uncovered a powerful new approach. The research, published in the journal Bioactive Materials, explores the synergistic effects of nitric oxide (NO) and hydrogen sulfide (H2S) in preventing thrombosis, offering a promising avenue for enhanced antithrombotic therapies.
Deng and his team developed an innovative codelivery system that targets the precise delivery of NO and H2S using an enzyme prodrug therapy (EPT) strategy. This method ensures that the prodrugs are specifically recognized by engineered β-galactosidase, allowing for targeted in vivo delivery. The results, confirmed through near-infrared fluorescence imaging and plasma and tissue level measurements, show that this targeted approach significantly reduces side effects associated with systemic delivery, such as prolonged bleeding time.
The study reveals that the combined delivery of NO and H2S at optimized levels results in a synergistic effect, effectively inhibiting platelet adhesion and activation. “The synergistic effect of NO and H2S is achieved through their cooperative enhancement of the cGMP level,” Deng explains. “This is accomplished via redox-based posttranslational modifications of phosphodiesterase 5A (PDE5A), which activates the cGMP/PKG signaling pathway.”
The implications of this research extend beyond the medical field, with potential commercial impacts for the energy sector. Thrombosis is not just a medical issue; it can also affect the efficiency and safety of energy production and distribution systems. For instance, blood clots can form in the pipelines and machinery of energy plants, leading to costly downtime and maintenance. By developing more effective antithrombotic therapies, this research could help mitigate such issues, ensuring smoother operations and reduced costs.
The study’s findings were further validated in two mouse models of FeCl3-induced arterial thrombosis and deep vein thrombosis, demonstrating enhanced therapeutic efficacy. “Our results confirm the synergistic efficacy of NO and H2S for antithrombotic therapy,” Deng states. “The codelivery system we developed represents a promising candidate for clinical translation.”
This research not only advances our understanding of thrombosis but also paves the way for future developments in the field. As Deng and his team continue to refine their codelivery system, the potential for clinical applications grows. The targeted delivery of NO and H2S could revolutionize antithrombotic therapies, offering a safer and more effective treatment option for patients worldwide. The study, published in Bioactive Materials, marks a significant step forward in the fight against thrombosis, with far-reaching implications for both medical and industrial sectors.
