Maria Francesca D'Ambrosio

Dilated cardiomyopathy (DCM) is the most common cardiomyopathy worldwide. Over the last few decades, significant progress has been made in understanding the genes responsible for DCM. A large number of variants have been detected, with heterogeneous distribution across the globe. Based on a systematic review of the available data, this review aims to investigate what we actually know about genetic, geographical and ethnic heterogeneity in DCM. What emerged is a disparity in clinical and instrumental valuations across different populations. Given the significant variability in the clinical and molecular presentation of these diseases, there is a need to develop an operational model that integrates technical and molecular diagnostics, imaging, and clinical capabilities tailored to the characteristics of different territories, while accounting for migratory flows and sex differences. By characterising specific genotypes, we could offer targeted therapies or contribute to the development of new care.

The mechanisms underlying obesity-related kidney disease are not well understood. Growing evidence suggests that free fatty acids (FFAs), a cause of oxidative stress, play an important role in obesity and its related complications. So, we decided to investigate, in a human-conditioned immortalized podocyte cell line, the capacity of physiopathological concentrations of 27nM of nonconjugated palmitate to induce intracellular reactive oxygen species (ROS) production, podocytes endoplasmic reticulum (ER) stress, podocytes inflammation, and mitochondrial dysfunction. A conditionally immortalized human podocyte cell line was exposed to different percentages of palmitate conjugated to bovine serum albumin (BSA) for 24h. We observed that palmitate, at the same concentrations seen in obese patients, caused overproduction of ROS in human podocytes and this oxidative stress induces dysfunctions in podocytes like inflammation and changes in profibrotic and lipotoxic markers. High-mobility group box 1 (HMGB1) is likely known to be a major mediator of ROS damaging effects, as its pharmacological inhibition prevents all ROS effects on podocytes. Our study shows how, in podocytes, an unbounded fraction of 27nM of palmitate can induce dysfunctions similar to that observed in obesity-related glomerulopathy (ORG). These results could contribute to elucidating underlying mechanisms contributing to the ORG pathogenesis.

These cases suggest that even if combined methylmalonic aciduria with homocystinuria is a rare entity, its identification is essential so as to allow the initiation of an effective early treatment to avoid the pathophysiological progression and the serious clinical consequences of this disease, even in cases of late-onset cblC

Over the last decades, the relevance of genetics in cardiovascular diseases has expanded, especially in the context of cardiomyopathies. Its relevance extends to the management of patients diagnosed with heart failure (HF), given its capacity to provide invaluable insights into the etiology of cardiomyopathies and identify individuals at a heightened risk of poor outcomes. Notably, the identification of an etiological genetic variant necessitates a comprehensive evaluation of the family lineage of the affected patients. In the future, these genetic variants hold potential as therapeutic targets with the capability to modify gene expression. In this complex setting, collaboration among cardiologists, specifically those specializing in cardiomyopathies and HF, and geneticists becomes paramount to improving individual and family health outcomes, as well as therapeutic clinical results. This review is intended to offer geneticists and cardiologists an updated perspective on the value of genetic research in HF and its implications in clinical practice.