Polymer Conjugation of Docosahexaenoic Acid Potentiates Cardioprotective Therapy in Preclinical Models of Myocardial Ischemia/Reperfusion Injury. Issue 9 (15th March 2021)

• Record Type: Journal Article
• Authors: Tejedor, Sandra; Dolz‐Pérez, Irene; Decker, Caitlin G.; Hernándiz, Amparo; Diez, Jose L.; Álvarez, Raquel; Castellano, Delia; García, Nahuel A.; Ontoria‐Oviedo, Imelda; Nebot, Vicent J.; González‐King, Hernán; Igual, Begoña; Sepúlveda, Pilar; Vicent, María J.
• Is Part Of: Advanced healthcare materials. Volume 10:Issue 9(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-03-15
• Subjects: cardioprotection -- ischemia/reperfusion injury -- polymer–drug conjugates -- polymer therapeutics -- polypeptides -- polyunsaturated fatty acids; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.202002121
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract: While coronary angioplasty represents an effective treatment option following acute myocardial infarction, the reperfusion of the occluded coronary artery can prompt ischemia–reperfusion (I/R) injury that significantly impacts patient outcomes. As ω ‐3 polyunsaturated fatty acids (PUFAs) have proven, yet limited cardioprotective abilities, an optimized polymer‐conjugation approach is reported that improves PUFAs bioavailability to enhance cardioprotection and recovery in animal models of I/R‐induced injury. Poly‐l ‐glutamic acid (PGA) conjugation improves the solubility and stability of di‐docosahexaenoic acid (diDHA) under physiological conditions and protects rat neonatal ventricular myocytes from I/R injury by reducing apoptosis, attenuating autophagy, inhibiting reactive oxygen species generation, and restoring mitochondrial membrane potential. Enhanced protective abilities are associated with optimized diDHA loading and evidence is provided for the inherent cardioprotective potential of PGA itself. Pretreatment with PGA–diDHA before reperfusion in a small animal I/R model provides for cardioprotection and limits area at risk (AAR). Furthermore, the preliminary findings suggest that PGA–diDHA administration in a swine I/R model may provide cardioprotection, limit edema and decrease AAR. Overall, the evaluation of PGA–diDHA in relevant preclinical models provides evidence for the potential of polymer‐conjugated PUFAs in the mitigation of I/R injury associated with coronary angioplasty. Abstract : An optimized poly‐l ‐glutamic acid‐based conjugate of the ω ‐3 polyunsaturated fatty acid di‐docosahexaenoic acid with adequate solution conformation enhances cardioprotection in preclinically relevant in vitro and small and large animal in vivo models after ischemia–reperfusion‐induced injury.