Polymer Conjugation of Docosahexaenoic Acid Potentiates Cardioprotective Therapy in Preclinical Models of Myocardial Ischemia/Reperfusion Injury

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.

The past, present, and future of breast cancer models for nanomedicine development

“…In the realm of nanomedicines, pig models have been used to evaluate cardioprotection [258] , chemotherapy-associated cardiotoxicity [259] , and hypersensitivity/infusion reactions (complement activation-related pseudoallergy) [260] , [261] . For example, Gyöngyösi et al compared the cardiotoxicity of doxorubicin and Myocet® in pigs by monitoring factors such as survival, body weight, and cardiac function [262] .…”

Topical Administration of a Marine Oil Rich in Pro-Resolving Lipid Mediators Accelerates Wound Healing in Diabetic db/db Mice through Angiogenesis and Macrophage Polarization

“…Interestingly, oral supplementation of fish oil increases the levels of these SPMs in patients with peripheral arterial disease (PAD) [ 34 ]. Beneficial effects of single molecules of these families or their substrates, for example, LXA4 (derived from AA) or resolvin D1 and D2 (derived from DHA), have been reported in animal models with different pathologies, including wound healing [ 25 , 35 , 36 , 37 , 38 ]. However, SPMs display non-redundant functions on different target cells, and thus it is difficult to envision that a single molecule could be sufficient to induce a complex pro-resolutive healing process in a clinical setting.…”

Nanomedicine‐Based Therapeutics for Myocardial Ischemic/Reperfusion Injury

“…Myocardial ischemic injury constitutes the universal leading cause of disability and death, which accounted for as much as DOI: 10.1002/adhm.202300161 1.72% of the global population. [1,2] Myocardial infarction (MI) is a major cardiovascular disease characterized by irreversible damage to cardiac contractility, ultimately leading to death. [3] Percutaneous coronary intervention and pharmaceutical drugs are commonly used to treat MI.…”