The Gene and Protein Expression of the Main Components of the Lipolytic System in Human Myocardium and Heart Perivascular Adipose Tissue. Effect of Coronary Atherosclerosis

• Main Authors: Małgorzata Knapp, Jan Górski, Janina Lewkowicz, Anna Lisowska, Monika Gil, Beata Wójcik, Tomasz Hirnle, Adrian Chabowski, Agnieszka Mikłosz
• Format: Article
• Language: English
• Published: MDPI AG 2020-01-01
• Series: International Journal of Molecular Sciences
• Subjects: perivascular adipose tissue; multivessel coronary artery disease; adipose triglyceride lipase; comparative gene identification-58; g0/g1 switch protein 2; hormone-sensitive lipase
• Online Access: https://www.mdpi.com/1422-0067/21/3/737

The aim of our study was to examine the regulation of triacylglycerols (TG) metabolism in myocardium and heart perivascular adipose tissue in coronary atherosclerosis. Adipose triglyceride lipase (ATGL) is the major TG-hydrolase. The enzyme is activated by a protein called comparative gene identification 58 (CGI-58) and inhibited by a protein called G0/G1 switch protein 2 (G0S2). Samples of the right atrial appendage and perivascular adipose tissue were obtained from two groups of patients: 1—with multivessel coronary artery disease qualified for coronary artery bypass grafting (CAD), 2—patients with no atherosclerosis qualified for a valve replacement (NCAD). The mRNA and protein analysis of ATGL, HSL, CGI-58, G0S2, FABP4, FAT/CD36, LPL, β-HAD, CS, COX4/1, FAS, SREBP-1c, GPAT1, COX-2, 15-LO, and NFκβ were determined by using real-time PCR and Western Blot. The level of lipids (i.e., TG, diacylglycerol (DG), and FFA) was examined by GLC. We demonstrated that in myocardium coronary atherosclerosis increases only the transcript level of G0S2 and FABP4. Most importantly, ATGL, β-HAD, and COX4/1 protein expression was reduced and it was accompanied by over double the elevation in TG content in the CAD group. The fatty acid synthesis and their cellular uptake were stable in the myocardium of patients with CAD. Additionally, the expression of proteins contributing to inflammation was increased in the myocardium of patients with coronary stenosis. Finally, in the perivascular adipose tissue, the mRNA of G0S2 was elevated, whereas the protein content of FABP-4 was increased and for COX4/1 diminished. These data suggest that a reduction in ATGL protein expression leads to myocardial steatosis in patients with CAD.