CONGRESS ABSTRACT

Metabolic syndrome (MetS) is a major predictor of adverse cardiac events associated with cardiac hypertrophy (CH). From a pathophysiological perspective, oxidative stress and redox status imbalance may play a pivotal role. In other pathological contexts, dysregulation of S-glutathionylation, a redox-dependent post-translational protein modification involving the conjugation of glutathione to cysteines, may contribute to oxidative injury and metabolic dysfunction. Experimental studies demonstrated that glutathionylated proteins (PSSG) may also have a role in regulating hypertrophic phenotype in cardiomyocytes, even though there is no evidence in patients. Hence, we aimed to depict the connection between CH and MetS and the role of PSSG in the CH development, in order to identify non-invasive biomarkers and potential targetable proteins.We conducted an observational case–control study involving non-syndromic overweight/obesity children aged 10–18 years with CH (cases) or without (controls). We collected anthropometric and biochemical parameters, cardiac data, levels of Apolipoprotein B (ApoB) and N-terminal pro B-type natriuretic peptide (NT-proBNP), and PSSG were evaluated in peripheral blood mononuclear cells (PBMCs) by mass spectrometry. To date, we have evaluated data from 43 paediatric patients, including 19 controls and 24 CH patients. No significant alterations in anthropometric and biochemical parameters were found between the two groups. Otherwise, children with CH exhibited significantly higher ApoB levels than controls. Although not significant, there is a trend toward higher NT-proBNP levels in cases than in controls, suggesting that the association may become statistically significant with a larger cohort. Notably, glutathionylation analysis in PBMCs in a cohort subgroup revealed differences in the pattern of glutathionylated proteins between controls and patients with CH. Specifically, among the 104 PSSG identified in the patient group, several key cytoskeletal proteins already known for their role in cardiac remodelling (e.g. α- and β-tubulin, tropomyosin A1, and tropomyosin 1) emerged.Our preliminary results suggest that patients with CH exhibit elevated ApoB levels, underscoring its central role in linking MetS and CH; moreover, the cardiac phenotype could be reflected in blood by evaluating glutathionylation of specific proteins. Further investigations are needed to support the translational relevance of our results.