Ignite Creation Date:
2024-05-06 @ 12:09 PM
Last Modification Date:
2024-10-26 @ 12:55 PM
Study NCT ID:
NCT03693261
Status:
COMPLETED
Last Update Posted:
2019-04-17
First Post:
2018-09-30
Brief Title:
Epicardial Fat in Coronary Artery Disease
Sponsor:
University of Miami
Organization:
University of Miami
Study Overview
Official Title:
Epicardial Fat as Brown Fat in Coronary Artery Disease
Status:
COMPLETED
Status Verified Date:
2019-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
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 followsSpecific Aims IaDoes human epicardial fat express makers of brown adipose tissue such UCP1 and brown adipocyte differentiation transcription factors in subjects with and without coronary artery diseasebDoes human epicardial fat express type 2 and type 3 deiodinase thyroid hormones and 3 adrenergic receptors in subjects with and without coronary artery diseasecIs the thermoregulatory function of the human epicardial fat correlated to the presence and severity of coronary artery disease Specific Aims IIaDoes the expression of brown fat and thyroid markers gene expression is higher in epicardial than subcutaneous fatbDoes epicardial fat thickness as measured by echocardiography correlate with the gene expression of brown adipose tissue and thyroid markerscDoes epicardial fat thickness as measured by echocardiography correlate with the presence and severity of coronary artery disease
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None