Epicardial adipocytes in the pathogenesis of atrial fibrillation: An update on basic and translational studies.

Epicardial adipose tissue (EAT) is an endocrine organ containing a host of cell types and undoubtedly serving a multitude of important physiologic functions. Aging and obesity cause hypertrophy of EAT. There is great interest in the possible connection between EAT and cardiovascular disease, in particular, atrial fibrillation (AF). Increased EAT is independently associated with AF and adverse events after AF ablation (e.g., recurrence of AF, and stroke). In general, the amount of EAT correlates with BMI or visceral adiposity. Yet on a molecular level, there are similarities and differences between epicardial and abdominal visceral adipocytes. In comparison to subcutaneous adipose tissue, both depots are enriched in inflammatory cells and chemokines, even in normal conditions. On the other hand, in comparison to visceral fat, epicardial adipocytes have an increased rate of fatty acid release, decreased size, and increased vascularity. Several studies have described an association between fibrosis of EAT and fibrosis of the underlying atrial myocardium. Others have discovered paracrine factors released from EAT that could possibly mediate this association. In addition to the adjacent atrial cardiomyocytes, EAT contains a robust stromal-vascular fraction and surrounds the ganglionic plexi of the cardiac autonomic nervous system (cANS). The importance of the cANS in the pathogenesis of atrial fibrillation is well known, and it is quite likely that there is feedback between EAT and the cANS. This complex interplay may be crucial to the maintenance of normal sinus rhythm or the development of atrial fibrillation. The extent the adipocyte is a microcosm of metabolic health in the individual patient may determine which is the predominant rhythm.

Depot-specific differences and insufficient subcutaneous adipose tissue angiogenesis in human obesity.

BACKGROUND: Adipose tissue expands in response to excess caloric intake, but individuals prone to deposit visceral instead of subcutaneous adipose tissue have higher risk of metabolic disease. The role of angiogenesis in the expandability of human adipose tissue depots is unknown. The objective of this study was to measure angiogenesis in visceral and subcutaneous adipose tissue and to establish whether there is a relationship between obesity, metabolic status, and the angiogenic properties of these depots. METHODS AND RESULTS: Angiogenic capacity was determined by quantifying capillary branch formation from human adipose tissue explants embedded in Matrigel, and capillary density was assessed by immunohistochemistry. Subcutaneous adipose tissue had a greater angiogenic capacity than visceral tissue, even after normalization to its higher initial capillary density. Gene array analyses revealed significant differences in expression of angiogenic genes between depots, including an increased subcutaneous expression of angiopoietin-like protein 4, which is proangiogenic in an adipose tissue context. Subcutaneous capillary density and angiogenic capacity decreased with morbid obesity, and subcutaneous, but not visceral, adipose tissue angiogenic capacity correlated negatively with insulin sensitivity. CONCLUSIONS: These data imply that subcutaneous adipose tissue has a higher capacity to expand its capillary network than visceral tissue, but this capacity decreases with morbid obesity. The decrease correlates with insulin resistance, suggesting that impairment of subcutaneous adipose tissue angiogenesis may contribute to metabolic disease pathogenesis.