Differences in Gene Expression and Gene Associations in Epicardial Fat Compared to Subcutaneous Fat

Abstract

Epicardial adipose tissue (EAT) plays a role in cardiac physiology and may contribute to the development of coronary artery disease. Our objective was to determine whether there was a significant difference in gene expression in EAT compared to subcutaneous adipose tissue (SAT) and to identify potential relationships. MEDLINE and EMBASE were searched using the key terms "Epicardial Adipose Tissue" or "Epicardial Fat" in combination with "RNA", "mRNA", or "gene". The entry criteria were studies that presented primary data including expression levels of mRNA in human EAT compared with SAT and an expression of variance (SD). Genes identified by 2 or more studies were evaluated. Genes that showed significant change in expression between EAT and SAT were examined using the Gene Functional Classification analytical tool in Database for Annotation, Visualization and Integrated Discovery and cross-validated by ToppGene. Seventeen genes were identified from 25 studies. Meta-analysis showed that 10 genes (ADORA1, adiponectin, AGT, ADM, CATA, IL-1β, MCP-1, RBP-4, TNF-α, UCP-1) were significantly different in EAT. Gene Functional Classification analysis yielded 23 clusters with significant relationships. The top clusters were focused on responses to glucocorticoid stimulus, regulation of apoptosis, cellular ion homeostasis, and responses to hormone stimulus. Genetic analysis shows that EAT is discretely different from SAT. ADORA1, adiponectin, AGT, ADM, CATA, IL-1β, MCP-1, RBP-4, TNF-α, and UCP-1 may play significant roles in the unique physiology of EAT and/or its role in pathophysiology, through mechanisms as diverse as steroid hormone responses and regulation of apoptosis.

Hypoxia‐inducible factor 1‐alpha (HIF‐1α) as a factor mediating the relationship between obesity and heart failure with preserved ejection fraction

“…Increased fibrosis within the epicardial adipose tissue depot is an important factor that will be discussed later. Second, epicardial fat can be a source of inflammatory cytokines whose production is accentuated in rapidly expanding adipocytes in obesity . Inflammation sets the stage for a fibrotic response.…”

“…The activation and transdifferentiation of fibroblasts into myofibroblasts and increased deposition of collagen leads to decreased capillary density and increased diffusion distance within the myocardium leading to extension of tissue hypoxia from adipose tissue into the myocardium. This tissue hypoxia then leads to failure of cardiovascular compensatory mechanisms that leads to decompensation of function and further disease …”

“…Second, epicardial fat can be a source of inflammatory cytokines whose production is accentuated in rapidly expanding adipocytes in obesity. [55][56][57][58] Inflammation sets the stage for a fibrotic response. Third, epicardial fat may contribute to myocardial fibrosis secondary to release of adipo-fibrokines, collagen I, III, and VI via a paracrine effect.…”

“…This tissue hypoxia then leads to failure of cardiovascular compensatory mechanisms that leads to decompensation of function and further disease. 58,90 Inflammation and resulting fibrosis are integral parts of the pathogenesis of diastolic dysfunction. HIF-1α plays a synergistic role with angiotensin II in the over expression of matrix metalloproteinases 2 and 9 (MMP 2 and 9).…”

Role of Epicardial Fat to Buffer Deformation and Vibration in Coronary Arteries

“…[1][2][3] Epicardial fat has genetic programs for production of substances such as adrenomedullin, adiponectin, and angiotensin-2 that have the potential to alter coronary artery vasoreactivity and possibly modulate the process of atherosclerosis. 4 A potentially very important proposed function of epicardial fat is "to buffer the coronary artery against the torsion induced by the arterial pulse wave and cardiac contraction or to offset rapid changes in the width of the blood vessels with arterial pulse." 1 Epicardial fat was proposed to also "limit the motion of the coronary arteries perhaps reducing the potential extremes of coronary artery velocity."…”