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Epicardial Adipose Tissue Removal Potentiates Outward Remodeling and Arrests Coronary Atherogenesis
Mikaela L. McKenney-Drake, PhD, Stacey D. Rodenbeck, PhD, Rebecca S. Bruning, PhD, Ayeeshik Kole, BS, Kyle W. Yancey, MD, Mouhamad Alloosh, MD, Harold S. Sacks, MD, Michael Sturek, PhD The Annals of Thoracic Surgery Volume 103, Issue 5, Pages (May 2017) DOI: /j.athoracsur Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions
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Fig 1 Protocol for removal of coronary epicardial adipose tissue (cEAT). (A) Diagram of coronary arteries depicting region of cEAT removal. (CFX = circumflex artery; LAD = left anterior descending coronary artery; LV = left ventricle; RCA = right coronary artery.) (B) After removal of cEAT, radioopaque ligation clips (black arrows) were placed near the surgery site. (C) Representative coronary angiogram obtained after the adipectomy procedure. Radioopaque ligation clips are visible markers of the adipectomy/sham site (black arrows). (LM = left main coronary artery.) (D) After euthanasia, adipectomy site was identified by location of ligation clips (black arrow). The Annals of Thoracic Surgery , DOI: ( /j.athoracsur ) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions
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Fig 2 Coronary epicardial adipose tissue resection (cEATx) attenuates coronary artery disease progression. (A) Representative intravascular ultrasonography (IVUS) stillframes at survival surgery (8 months [mos]) and euthanasia (11 months). (Right panels) The IVUS was verified with Verhoeff-Van Gieson histology. Red dashed line indicates external elastic lamina; yellow dotted line indicates lumen; white dots are placed 1 mm apart. (B) The cEATx significantly attenuates coronary artery disease progression, as assessed by percent stenosis (p < 0.05). (C) The IVUS measurement of percent stenosis correlates with histologic measurement of percent stenosis, verifying IVUS assessment of coronary artery disease severity. The Annals of Thoracic Surgery , DOI: ( /j.athoracsur ) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions
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Fig 3 Coronary epicardial adipose tissue resection (cEATx) does not alter plaque size, but attenuates intimal cell proliferation. (A) Representative sham-operated intimal section stained with Ki-67; black arrows indicate positive staining. (B) Representative cEATx intimal section stained with Ki-67; black arrows indicate positive staining. (C) Intimal cell proliferation was reduced in cEATx arteries, compared with shams (p < 0.05). (D) Plaque area significantly increased after survival procedure in sham operated animals (p < 0.05), but was unchanged in cEATx swine (p = 0.2). Solid bars indicate survival; open bars indicate euthanasia. The Annals of Thoracic Surgery , DOI: ( /j.athoracsur ) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions
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Fig 4 Expression of inflammatory markers is unaltered by coronary epicardial adipose tissue resection (cEATx). (A–H) Representative images of macrophage scavenger receptor-A (MSR-A) and T-cadherin stained (A, C, E, G) arterial and (B, D, F, H) adipose sections from (A–D) sham operated and (E–H) cEATx operated swine. (I) MSR-A expression within atherosclerotic plaques is unchanged by cEATx operation. (J) MSR-A expression within adipose tissue is unchanged by cEATx operation. (K) T-cadherin expression within atherosclerotic plaques is unchanged by cEATx operation. (L) T-cadherin expression within adipose tissue is unchanged by cEATx operation. The Annals of Thoracic Surgery , DOI: ( /j.athoracsur ) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions
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Fig 5 The Glagov phenomenon is potentiated with coronary epicardial adipose tissue resection (cETAx). (A, B) Removal of cEAT shifts the relationship between external elastic lamina (EEL) area and plaque area, thus potentiating outward remodeling during plaque growth. Red indicates cEATx; black indicates sham. (C) Outward remodeling, as assessed by the change in EEL area from survival to sacrifice, was increased in cEATx swine, compared with shams (p < 0.05). (D) Graphic representation of the EEL/plaque area slope. Outward remodeling is reduced with coronary artery disease progression in sham-operated swine (p < 0.05), but is preserved after cEATx (p = 0.4). Solid bars indicate survival; open bars indicate euthanasia. The Annals of Thoracic Surgery , DOI: ( /j.athoracsur ) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions
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Fig 6 Coronary epicardial adipose tissue resection (cEATx) results in significant outward remodeling and increases lumen diameter. (A) The cEATx animals had an expansion in lumen size after surgery (p < 0.05). This expansion was not observed in sham-operated animals (p = 0.4). Solid bars indicate survival; open bars indicate euthanasia. (B) During normal (sham) coronary artery disease progression, plaque area increased with little change in external elastic lamina (EEL) area, resulting in increased coronary stenosis. (C) After cEATx, significant outward remodeling is observed as an increase in EEL area. This, combined with inhibition of increases in plaque size, results in an increased lumen area, thus reducing percent stenosis. The Annals of Thoracic Surgery , DOI: ( /j.athoracsur ) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions
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