Key result
Coronary atherosclerosis is linked to ~20% lower myocardial ATGL expression and increased lipid accumulation.
Why the study?
The study was conducted to examine the regulation of triacylglycerols metabolism in myocardium and heart perivascular adipose tissue in coronary atherosclerosis.
Does severe coronary atherosclerosis alter the expression of the triacylglycerol lipolytic system (ATGL, CGI-58, G0S2) and lipid content in human myocardium and perivascular adipose tissue compared to patients without coronary atherosclerosis?
Case-Control (n=53)
No
Does severe coronary atherosclerosis alter the expression of the triacylglycerol lipolytic system (ATGL, CGI-58, G0S2) and lipid content in human myocardium and perivascular adipose tissue compared to patients without coronary atherosclerosis?
p-value: p=<0.05
This study provides the first human tissue evidence that coronary atherosclerosis is associated with reduced myocardial ATGL protein expression and reduced beta-oxidation enzyme levels, leading to marked myocardial triacylglycerol accumulation (steatosis) and increased local inflammatory signaling.
Myocardial steatosis may accompany CAD; extends animal data to human tissue but leaves causal and therapeutic roles open.
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.
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Knapp et al. (2020) conducted a case-control in Multivessel coronary artery disease (CAD) (n=53). Multivessel coronary artery disease (coronary atherosclerosis) vs. Absence of coronary atherosclerosis (patients undergoing mitral or aortic valve replacement) was evaluated on Myocardial adipose triglyceride lipase (ATGL) protein expression and triacylglycerol (TG) content in right atrial appendage and perivascular adipose tissue (p=<0.05). Coronary atherosclerosis reduced myocardial ATGL protein expression by 20% (p<0.05) and increased myocardial triacylglycerol content by 121% (p<0.05) compared to non-atherosclerotic controls.
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