Epicardial Fat in Coronary Artery Disease
Epicardial Fat in Coronary Artery Disease
We hypothesize that human epicardial fat plays a thermogenic role to the myocardium. We
 hypothesize that epicardial fat may express genes of brown fat and thyroid function that are
 down-regulated by the presence of coronary artery disease. Because the postulated metabolic
 role of the epicardial fat, we also hypothesize that the gene expression of these regulatory
 thermogenic factors is higher in epicardial than subcutaneous fat

 This will be a cross-sectional study conducted over a one-year period in patients with or
 without coronary artery disease who require elective cardiac surgery regardless their
 participation in the study.

 Study group will be formed by 50 patients with clinically and angiographically established
 CAD who will undergo coronary artery bypass graft, as part of their standard medical care.
 Control group will be formed by 10 subjects, randomly selected, who will undergo cardiac
 surgery for aortic or mitral valve replacement as part of their standard medical care (these
 patients have no history, clinical signs of CAD, and show normal coronary arteries on
 coronary angiography).

 This will be a cross-sectional study conducted over a one-year period in patients with or
 without coronary artery disease who require elective cardiac surgery regardless their
 participation in the study.

 Adipose tissue will be collected during the cardiac surgery.
Our previous studies indicate that epicardial fat, the visceral fat depot of the heart, plays
 a role in modulating the heart morphology and its function (Iacobellis et al 2005). Notably,
 no muscle fascia divides the epicardial fat and the myocardium and the two tissues share the
 same microcirculation (Iacobellis et al 2005). Epicardial fat has peculiar biochemical
 properties and is actively involved in lipid and energy homeostasis. Epicardial fat is also a
 source of several bioactive molecules that might directly influence the myocardium and
 coronary arteries (Iacobellis et al, 2005,). Because of its anatomic proximity to the
 myocardium and its intense paracrine and metabolic activity, it is suggested that epicardial
 fat cytokines reach the myocardium through paracrine or vasocrine pathways and consequently
 modify its function. Given all these effects and properties, epicardial fat is
 pathophysiologically and clinically related to development and progression of coronary artery
 disease and atherosclerosis, regardless of obesity (Iacobellis 2010). Additionally,
 epicardial fat directly correlates with the intramyocardial lipid content, as we recently
 described (Malavazos 2010), suggesting a real interaction between the two tissues. However, a
 dichotomous role has been actually attributed to the epicardial fat. In fact, under
 physiological conditions epicardial fat displays cardioprotective effects (Iacobellis 2009)
 and potentially energetic and thermogenic properties, as brown fat (Sacks 2009). Although the
 interpretation of this finding is still unclear, expression of uncoupling protein1 (UCP1), a
 marker of brown fat, has been found in human epicardial fat and significantly higher than in
 subcutaneous fat. We know that brown fat generates heat in response to cold temperatures and
 activation of the autonomic nervous system under the direct control of thyroid hormones
 (Bianco 2011). Although the interest in brown fat in humans is growing, our understanding of
 its actual role in humans is still unclear. The heart is a highly demand organ, under the
 metabolic control of the thyroid and possibly the epicardial fat. Interestingly experimental
 models show that hypoxia induces type 3 deiodinase (D3) overexpression in the myocardium that
 inactivates T3 during ischemia, to protectively decrease cardiomyocytes metabolism and energy
 expenditure (Simonides et al 2008). Epicardial fat may function like brown fat and thyroid
 target tissue to protect and defend the myocardium and coronary artery against hypothermia
 and chronic hypoxia. Nevertheless, whether epicardial fat may have this role and whether this
 may be affected by the presence of coronary artery disease is currently unknown. We therefore
 hypothesize that human epicardial fat plays a thermogenic role to the myocardium. We
 hypothesize that epicardial fat may express genes of brown fat and thyroid function that are
 downregulated by the presence of coronary artery disease. Because the postulated metabolic
 role of the epicardial fat, we also hypothesize that the gene expression of these regulatory
 thermogenic factors is higher in epicardial than subcutaneous fat. These hypotheses will be
 tested as follows:Specific Aims Ia)Does human epicardial fat express makers of brown adipose
 tissue, such UCP1 and brown adipocyte differentiation transcription factors in subjects with
 and without coronary artery disease?b)Does human epicardial fat express type 2 and type 3
 deiodinase, thyroid hormones and 3 adrenergic receptors in subjects with and without coronary
 artery disease?c)Is the thermoregulatory function of the human epicardial fat correlated to
 the presence and severity of coronary artery disease? Specific Aims IIa)Does the expression
 of brown fat and thyroid markers gene expression is higher in epicardial than subcutaneous
 fat?b)Does epicardial fat thickness, as measured by echocardiography, correlate with the gene
 expression of brown adipose tissue and thyroid markers?c)Does epicardial fat thickness, as
 measured by echocardiography, correlate with the presence and severity of coronary artery
 disease?
Inclusion Criteria:

 Subjects with clinically and angiographically established CAD

 Controls: subjects with have no history, clinical signs of CAD, and show normal coronary
 arteries on coronary angiography, who will undergo cardiac surgery for aortic or mitral
 valve replacement as part of their standard medical care

 Exclusion Criteria:

 Patients with heart failure, kidney failure or liver failure, infective disease or cancer
 will be excluded from the study. Subjects taking glucocorticoids or estrogens or patients
 currently smoking will be excluded from the study. Patients with mental disorders will also
 not be included