Mikaela L McKenney-Drake1, Stacey D Rodenbeck2, Rebecca S Bruning3, Ayeeshik Kole4, Kyle W Yancey5, Mouhamad Alloosh2, Harold S Sacks6, Michael Sturek7. 1. Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana; Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana. 2. Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana. 3. Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana; College of Pharmacy and Health Sciences, Butler University, Indianapolis, Indiana. 4. Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana; Covance, Inc, Greenfield, Indiana. 5. Weldon School of Biomedical Engineering, Purdue University, Lafayette, Indiana. 6. Endocrinology and Diabetes Division, VA Greater Los Angeles Healthcare System, and David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. 7. Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana; Covance, Inc, Greenfield, Indiana. Electronic address: msturek@iu.edu.
Abstract
BACKGROUND: Pericoronary epicardial adipose tissue (cEAT) serves as a metabolic and paracrine organ that contributes to inflammation and is associated with macrovascular coronary artery disease (CAD) development. Although there is a strong correlation in humans between cEAT volume and CAD severity, there remains a paucity of experimental data demonstrating a causal link of cEAT to CAD. The current study tested the hypothesis that surgical resection of cEAT attenuates inflammation and CAD progression. METHODS: Female Ossabaw miniature swine (n = 12) were fed an atherogenic diet for 8 months and randomly allocated into sham (n = 5) or adipectomy (n = 7) groups. Both groups underwent a thoracotomy, opening of the pericardial sac, and placement of radioopaque clips to mark the proximal left anterior descending artery. Adipectomy swine underwent removal of 1 to 1.5 cm2 of cEAT from the proximal artery. After sham or adipectomy, CAD severity was assessed with intravascular ultrasonography. Swine recovered for an additional 3 months on an atherogenic diet, and CAD was assessed immediately before euthanasia. Artery sections were processed for histologic and immunohistochemical analysis. RESULTS: Severity of CAD as assessed by percent stenosis was reduced in the adipectomy cohort compared with shams; however, plaque size remained unaltered, whereas larger plaque sizes developed in sham-operated swine. Adipectomy resulted in an expanded arterial diameter, similar to the Glagov phenomenon of positive outward remodeling. No differences in inflammatory marker expression were observed. CONCLUSIONS: These data indicate that cEAT resection did not alter inflammatory marker expression, but arrested CAD progression through increased positive outward remodeling and arrest of atherogenesis.
BACKGROUND: Pericoronary epicardial adipose tissue (cEAT) serves as a metabolic and paracrine organ that contributes to inflammation and is associated with macrovascular coronary artery disease (CAD) development. Although there is a strong correlation in humans between cEAT volume and CAD severity, there remains a paucity of experimental data demonstrating a causal link of cEAT to CAD. The current study tested the hypothesis that surgical resection of cEAT attenuates inflammation and CAD progression. METHODS: Female Ossabaw miniature swine (n = 12) were fed an atherogenic diet for 8 months and randomly allocated into sham (n = 5) or adipectomy (n = 7) groups. Both groups underwent a thoracotomy, opening of the pericardial sac, and placement of radioopaque clips to mark the proximal left anterior descending artery. Adipectomy swine underwent removal of 1 to 1.5 cm2 of cEAT from the proximal artery. After sham or adipectomy, CAD severity was assessed with intravascular ultrasonography. Swine recovered for an additional 3 months on an atherogenic diet, and CAD was assessed immediately before euthanasia. Artery sections were processed for histologic and immunohistochemical analysis. RESULTS: Severity of CAD as assessed by percent stenosis was reduced in the adipectomy cohort compared with shams; however, plaque size remained unaltered, whereas larger plaque sizes developed in sham-operated swine. Adipectomy resulted in an expanded arterial diameter, similar to the Glagov phenomenon of positive outward remodeling. No differences in inflammatory marker expression were observed. CONCLUSIONS: These data indicate that cEAT resection did not alter inflammatory marker expression, but arrested CAD progression through increased positive outward remodeling and arrest of atherogenesis.
Authors: G S Mintz; S E Nissen; W D Anderson; S R Bailey; R Erbel; P J Fitzgerald; F J Pinto; K Rosenfield; R J Siegel; E M Tuzcu; P G Yock Journal: J Am Coll Cardiol Date: 2001-04 Impact factor: 24.094
Authors: Amir A Mahabadi; Marie H Berg; Nils Lehmann; Hagen Kälsch; Marcus Bauer; Kaffer Kara; Nico Dragano; Susanne Moebus; Karl-Heinz Jöckel; Raimund Erbel; Stefan Möhlenkamp Journal: J Am Coll Cardiol Date: 2013-02-20 Impact factor: 24.094
Authors: Zachary P Neeb; Jason M Edwards; Mouhamad Alloosh; Xin Long; Eric A Mokelke; Michael Sturek Journal: Comp Med Date: 2010-08 Impact factor: 0.982
Authors: Hikmet Yorgun; Uğur Canpolat; Tuncay Hazırolan; Ahmet Hakan Ateş; Hamza Sunman; Muhammet Dural; Levent Şahiner; Ergün Barış Kaya; Kudret Aytemir; Lale Tokgözoğlu; Giray Kabakçı; Ali Oto Journal: Int J Cardiol Date: 2011-09-16 Impact factor: 4.164
Authors: Alyssa K Phillips-Eakley; Mikaela L McKenney-Drake; Martin Bahls; Sean C Newcomer; John S Radcliffe; Meryl E Wastney; William G Van Alstine; George Jackson; Mouhamad Alloosh; Berdine R Martin; Michael Sturek; Connie M Weaver Journal: J Am Heart Assoc Date: 2015-08-13 Impact factor: 5.501
Authors: Sarah R Anthony; Adrienne R Guarnieri; Anamarie Gozdiff; Robert N Helsley; Albert Phillip Owens; Michael Tranter Journal: Clin Sci (Lond) Date: 2019-11-29 Impact factor: 6.124
Authors: Jill K Badin; Ayeeshik Kole; Benjamin Stivers; Victor Progar; Anisha Pareddy; Mouhamad Alloosh; Michael Sturek Journal: J Transl Med Date: 2018-03-09 Impact factor: 5.531
Authors: Milton Packer; Carolyn S P Lam; Lars H Lund; Mathew S Maurer; Barry A Borlaug Journal: Eur J Heart Fail Date: 2020-06-26 Impact factor: 15.534