Cardiovascular diseases, including myocardial infarction (MI), represent the main worldwide cause of mortality and morbidity. In this scenario, to contrast the irreversible damages following MI, cardiac regeneration has emerged as a novel and promising solution for in situ cellular regeneration, preserving cell behavior and tissue cytoarchitecture. Among the huge variety of natural, synthetic, and hybrid compounds used for tissue regeneration, alginate emerged as a good candidate for cellular preservation and delivery, becoming one of the first biomaterial tested in pre-clinical research and clinical trials concerning cardiovascular diseases. Although promising results have been obtained, recellularization and revascularization of the infarcted area present still major limitations. Therefore, the demand is rising for alginate functionalization and its combination with molecules, factors, and drugs capable to boost the regenerative potential of the cardiac tissue. The focus of this review is to elucidate the promising properties of alginate and to highlight its benefits in clinical trials in relation to cardiac regeneration. The definition of hydrogels, the alginate characteristics, and recent biomedical applications are herewith described. Afterward, the review examines in depth the ongoing developments to refine the material relevance in cardiac recovery and regeneration after MI and presents current clinical trials based on alginate.

Arrhythmogenic cardiomyopathy (ACM) is hallmarked by ventricular fibro-adipogenic alterations, contributing to cardiac dysfunctions and arrhythmias. Although genetically determined (e.g., PKP2 mutations), ACM phenotypes are highly variable. More data on phenotype modulators, clinical prognosticators, and etiological therapies are awaited. We hypothesized that oxidized low-density lipoprotein (oxLDL)-dependent activation of PPARc, a recognized effector of ACM adipogenesis, contributes to disease pathogenesis. ACM patients showing high plasma concentration of oxLDL display severe clinical phenotypes in terms of fat infiltration, ventricular dysfunction, and major arrhythmic event risk. In ACM patient-derived cardiac cells, we demonstrated that oxLDLs are major cofactors of adipogenesis. Mechanistically, the increased lipid accumulation is mediated by oxLDL cell internalization through CD36, ultimately resulting in PPARc upregulation. By boosting oxLDL in a Pkp2 heterozygous knock-out mice through high-fat diet feeding, we confirmed in vivo the oxidized lipid dependency of cardiac adipogenesis and right ventricle systolic impairment, which are counteracted by atorvastatin treatment. The modulatory role of oxidized lipids on ACM adipogenesis, demonstrated at cellular, mouse, and patient levels, represents a novel risk stratification tool and a target for ACM pharmacological strategies.

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