AUTHOR=Infante Teresa , Forte Ernesto , Aiello Marco , Salvatore Marco , Cavaliere Carlo 

TITLE=In Vivo and In Vitro Analysis in Coronary Artery Disease Related to Type 2 Diabetes

JOURNAL=Frontiers in Endocrinology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2017.00209

DOI=10.3389/fendo.2017.00209

ISSN=1664-2392

ABSTRACT=<sec id="ST1"><title>Aim</title><p>The leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (DM) is coronary artery disease (CAD), a condition often asymptomatic but severe in these patients. Although glucose metabolism impairment and oxidative stress are known actors in the endothelial dysfunction/remodeling that occurs in diabetic patients, the relationship between cardiovascular disorders and DM is not fully understood. We have performed both an <italic>in vivo</italic> imaging and <italic>in vitro</italic> molecular analysis to investigate diabetic-specific CAD alterations.</p></sec><sec id="ST2"><title>Methods</title><p>Computed tomography coronary angiography (CTCA) was performed in a group of 20 diabetic patients with CAD (DM<sup>+</sup>CAD<sup>+</sup>), 20 non-diabetic with CAD (DM<sup>−</sup>CAD<sup>+</sup>), 10 diabetic non-CAD patients (DM<sup>+</sup>CAD<sup>−</sup>), and 20 non-diabetic healthy subjects (HS). Imaging quantitative parameters such as calcium score (Cascore), calcified plaque volume (CPV), non-calcified plaque volume (NCPV), total plaque volume (TPV), remodeling index (RI), and plaque burden were extracted for each CAD subject. Moreover, the expression levels of superoxide dismutase 2 (SOD2) and liver X receptor alpha (LXRα) genes were analyzed in the peripheral blood mononuclear cells, whereas hyaluronan (HA) concentrations were evaluated in the plasma of each subject.</p></sec><sec id="ST3"><title>Results</title><p>Imaging parameters, such as Cascore, CPV, RI, and plaque burden, were significantly higher in DM<sup>+</sup>CAD<sup>+</sup> group, compared to DM<sup>−</sup>CAD<sup>+</sup> (<italic>P</italic> = 0.019; <italic>P</italic> = 0.014; <italic>P</italic> &lt; 0.001, <italic>P</italic> &lt; 0.001, respectively). SOD2 mRNA was downregulated, while LXRα gene expression was upregulated in DM<sup>+</sup>CAD<sup>−</sup>, DM<sup>+</sup>CAD<sup>+</sup>, and DM<sup>−</sup>CAD<sup>+</sup> groups compared to HS (<italic>P</italic> = 0.001, <italic>P</italic> = 0.03, and <italic>P</italic> = 0.001 for SOD2 and <italic>P</italic> = 0.006, <italic>P</italic> = 0.008, and <italic>P</italic> &lt; 0.001 for LXRα, respectively). Plasmatic levels of HA were higher in DM<sup>−</sup>CAD<sup>+</sup>, DM<sup>+</sup>CAD<sup>−</sup>, and DM<sup>+</sup>CAD<sup>+</sup> groups, compared to HS (<italic>P</italic> = 0.001 for the three groups). When compared to DM<sup>−</sup>CAD<sup>+</sup>, HA concentration was higher in DM<sup>+</sup>CAD<sup>−</sup> (<italic>P</italic> = 0.008) and DM<sup>+</sup>CAD<sup>+</sup> (<italic>P</italic> &lt; 0.001) with a significant difference between the two diabetic groups (<italic>P</italic> = 0.003). Moreover, HA showed a significant association with diabetes (<italic>P</italic> = 0.01) in the study population, and the correlation between HA levels and glycemia was statistically significant (ρ = 0.73, <italic>P</italic> &lt; 0.001).</p></sec><sec id="ST4"><title>Conclusion</title><p>In our population, imaging parameters highlight a greater severity of CAD in diabetic patients. Among molecular parameters, HA is modulated by diabetic CAD-related alterations while SOD2 and LXRα are found to be more associated with CAD but do not discriminate between diabetic and non-diabetic subgroups.</p></sec>