368-P: Type 2 Diabetes Mellitus Increases Epicardial Adipose Tissue Senescence in Subjects with Coronary Artery Disease during Elective Cardiac Surgery

• Published in: Diabetes (New York, N.Y.) Vol. 70; no. Supplement_1
• Main Authors: MRAZ, MILOS, TRNOVSKA, JAROSLAVA, KASPEROVA, BARBORA JUDITA, DVORAKOVA, IVETA, LACINOVA, ZDENKA, HLAVACEK, DANIEL, MAHRIK, JAKUB, IVAK, PETER, NETUKA, IVAN, HALUZIK, MARTIN
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01.06.2021
• Subjects: Adipose tissue; Cardiovascular disease; Cardiovascular diseases; Coronary artery; Coronary artery disease; Coronary vessels; Cyclin-dependent kinase inhibitor p21; Diabetes; Diabetes mellitus (non-insulin dependent); Gene expression; Heart diseases; Heart surgery; Myocardium; Senescence
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db21-368-P

Cellular senescence is a novel mechanism suggested to contribute to the development of type 2 diabetes mellitus (T2DM) and cardiovascular diseases. Here, we analyzed the expression of senescent markers in myocardium and adjacent adipose tissue of subjects with and without coronary artery disease (CAD) and T2DM undergoing elective cardiac surgery. Eleven subjects with CAD and T2DM (DM group), 13 subjects with CAD without T2DM (CAD group) and 8 subjects without both CAD and T2DM (C - control) group undergoing elective cardiac surgery (CABG and/or valvular surgery) were included into the study. Samples of subcutaneous (SAT) and epicardial (EAT) adipose tissue and myocardium form right atrial wall were taken along with standard biochemical and anthropometric parameters at the beginning and end of surgery. mRNA expression of senescent markers p21 and p16 was assessed using qRT PCR. All 3 groups did not differ with respect to age (65.2 ± 6.9 vs. 61.7 ± 9.8 vs. 57.9 ± 12.3 years for DM vs. CAD vs. C, n.s.) or BMI (30.8 ± 3.9 vs. 28.5 ± 3.9 vs. 30.2 ± 3.4 kg/m2, n.s.), while DM group showed higher levels of fasting glucose (8.4 ± 1.6 vs. 5.9 ± 1.1 vs. 5.9 ± 0.9 mmol/, p=0.005) and HbA1C (52.5 ± 8.9 vs. 38.9 ± 4.2 vs. 31.5 ± 8.9 mmol/mol, p<0.001) relative to others. At the beginning of surgery no difference in mRNA expression of either factor could be seen in any of the examined tissues except of increased expression of p16 in the myocardium of CAD group (p=0.044 vs. C group). In DM subjects, cardiac surgery significantly increased mRNA expression of p21 in myocardium (p=0.15 vs. C and CAD group) and EAT (p=0.002 vs. C group), while not such change could be seen in the nondiabetic CAD and C group. To conclude, in CAD subjects T2DM is associated with increased cellular senescence in EAT and myocardium during elective cardiac surgery. This mechanism might at least partially explain the more detrimental outcomes of CAD patients with as compared to without T2DM.