Epicardial Fat in Coronary Artery Disease
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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?
    

Intervention name(s): Coronary artery bypass grafting (CABG); Valve replacement
Intervention type(s): Procedure; Procedure
Intervention description(s): CABG, as part of the standard medical care; cardiac surgery for aortic or mitral valve replacement as part of their standard medical care
Observational model: Case-Crossover
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        The total number of patients participating in the research will be 60. The study group will
        be formed by 50 consecutive patients, male and female, age 50-75 years, Caucasian, Hispanic
        and African American, patients with clinically and angiographically established CAD who
        will undergo CABG, as part of their standard medical care. The control group will be formed
        by 10 subjects male and female age 50-75 years, 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.
      
Biospecimen description: 
      Adipose tissue will be collected during the cardiac surgery. Epicardial adipose tissue (EAT)
      biopsy samples (average 0.5-1.0 g) will be taken by cardiac surgeon after anesthesia, before
      heparin administration, near the proximal tract of the right coronary artery. Each tissue
      sample will be snap frozen in liquid nitrogen and stored at -80 °C until analysis in a
      freezer . The subcutaneous fat tissue (SAT) will be harvested at the site of the thoracic
      wound and preserved in the same manner.
    
Keywords: epicardial fat