Apolipoprotein b level elevation and glutathionylated proteins as new biomarkers for cardiac hypertrophy in children
S Di Marzio, N Cantarutti, M Bianchi, F Grignaffini, N Panera, G Andolina, A Pastore, A Alisi, M SilvettiAbstract
Background
Obesity leads to a series of pathophysiological alterations collectively referred to as metabolic syndrome (MS), thus making youngs and adults susceptible to an increased risk of cardiovascular events, including hypertension and cardiac hypertrophy (CH). In patients with MS, high levels of Apolipoprotein B (ApoB) and the imbalance of redox homeostasis are common mechanisms underlying MS and cardiovascular risk, but there is a little evidence that they may also play a role in the connection between MS traits and CH. Notably, among the multiple oxidative mechanisms, protein glutathionylation has recently emerged as a key regulator of the hypertrophic phenotype in cardiomyocytes, although it lacks evidence in patients.
Purpose
The primary objective of our study is to investigate whether levels of ApoB and glutathionylated proteins (ProSSG) can serve as proxy markers of CH in overweight/obese paediatric patients.
Methods
We designed an observational study enrolling 43 non-syndromic overweight/obese children (aged range, 10–18 years), of whom 44% (N=19) had no CH (CTRL), while 56% (N=24) had CH. We collected: i) anthropometric and biochemical parameters; ii) cardiac data; and iii) blood samples to evaluate ApoB and N-terminal pro B-type natriuretic peptide (NT-proBNP) by commercially available assays, and ProSSG levels in peripheral blood mononuclear cells (PBMCs) by mass spectrometry.
Results
Our results revealed no significant differences in anthropometric and biochemical parameters between CTRL and CH patients. On the contrary, we found that ApoB (p<0.05) and NT-proBNP (not significantly) levels were increased in the CH group compared to the CTRL group. Moreover, mass spectrometry analysis of the ProSSG pattern revealed that glutathionylation of 104 proteins occurred only in children with CH. Among these ProSSG proteins, it emerged that cytoskeletal (such as alpha and beta tubulin) and sarcomeric (such as tropomyosin A1 and tropomyosin 1) proteins were present.
Conclusions
Our preliminary findings demonstrated that individuals with CH have higher ApoB and NT-proBNP levels, suggesting a possible role in pathogenetically linking MetS and CH. Additionally, the cardiac phenotype may be reflected in blood by assessing ProSSG levels. To confirm the translational applicability of our findings, a further study in a larger cohort is necessary.