Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Journal of Cardiothoracic Surgery
Published in: Journal of Cardiothoracic Surgery 1/2014

Open Access 01-12-2014 | Research article

Epicardial adipose excision slows the progression of porcine coronary atherosclerosis

Authors: Mikaela L McKenney, Kyle A Schultz, Jack H Boyd, James P Byrd, Mouhamad Alloosh, Shawn D Teague, Arturo A Arce-Esquivel, John N Fain, M Harold Laughlin, Harold S Sacks, Michael Sturek

Published in: Journal of Cardiothoracic Surgery | Issue 1/2014

Login to get access

Abstract

Background

In humans there is a positive association between epicardial adipose tissue (EAT) volume and coronary atherosclerosis (CAD) burden. We tested the hypothesis that EAT contributes locally to CAD in a pig model.

Methods

Ossabaw miniature swine (n = 9) were fed an atherogenic diet for 6 months to produce CAD. A 15 mm length by 3–5 mm width coronary EAT (cEAT) resection was performed over the middle segment of the left anterior descending artery (LAD) 15 mm distal to the left main bifurcation. Pigs recovered for 3 months on atherogenic diet. Intravascular ultrasound (IVUS) was performed in the LAD to quantify atheroma immediately after adipectomy and was repeated after recovery before sacrifice. Coronary wall biopsies were stained immunohistochemically for atherosclerosis markers and cytokines and cEAT was assayed for atherosclerosis-related genes by RT-PCR. Total EAT volume was measured by non-contrast CT before each IVUS.

Results

Circumferential plaque length increased (p < 0.05) in the proximal and distal LAD segments from baseline until sacrifice whereas plaque length in the middle LAD segment underneath the adipectomy site did not increase. T-cadherin, scavenger receptor A and adiponectin were reduced in the intramural middle LAD. Relative to control pigs without CAD, 11β-hydroxysteroid dehydrogenase (11βHSD-1), CCL19, CCL21, prostaglandin D2 synthase, gp91phox [NADPH oxidase], VEGF, VEGFGR1, and angiotensinogen mRNAs were up-regulated in cEAT. EAT volume increased over 3 months.

Conclusion

In pigs used as their own controls, resection of cEAT decreased the progression of CAD, suggesting that cEAT may exacerbate coronary atherosclerosis.

Literature
  1. Ouwens DM, Sell H, Greulich S, Eckel J: The role of epicardial and perivascular adipose tissue in the pathophysiology of cardiovascular disease. J Cell Mol Med. 2010, 14: 2223-2234. 10.1111/j.1582-4934.2010.01141.x.View ArticlePubMedPubMed Central
  2. Verhagen SN, Visseren FLJ: Perivascular adipose tissue as a cause of atherosclerosis. Atherosclerosis. 2011, 214: 3-10. 10.1016/j.atherosclerosis.2010.05.034.View ArticlePubMed
  3. Iozzo P: Myocardial, perivascular, and epicardial fat. Diabetes Care. 2011, 34: S371-S379. 10.2337/dc11-s250.View ArticlePubMedPubMed Central
  4. Ding J, Hsu FC, Harris TB, Liu Y, Kritchevsky SB, Szklo M, Ouyang P, Espeland MA, Lohman KK, Criqui MH, Allison M, Bluemke DA, Carr JJ: The association of pericardial fat with incident coronary heart disease: the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr. 2009, 90: 499-504. 10.3945/ajcn.2008.27358.View ArticlePubMedPubMed Central
  5. Tamarappoo B, Dey D, Shmilovich H, Nakazato R, Gransar H, Cheng VY, Friedman JD, Hayes SW, Thomson LEJ, Slomka PJ, Rozanski A, Berman DS: Increased pericardial fat volume measured from noncontrast CT predicts myocardial ischemia by SPECT. J Am Coll Cardiol Img. 2010, 3: 1104-1112. 10.1016/j.jcmg.2010.07.014.View Article
  6. Cheng VY, Dey D, Tamarappoo B, Nakazato R, Gransar H, Miranda-Peats R, Ramesh A, Wong ND, Shaw LJ, Slomka PJ, Berman DS: Pericardial fat burden on ECG-gated noncontrast CT in asymptomatic patients who subsequently experience adverse cardiovascular events. J Am Coll Cardiol Img. 2010, 3: 352-360. 10.1016/j.jcmg.2009.12.013.View Article
  7. Mazurek T, Zhang L, Zalewski A, Mannion JD, Diehl JT, Arafat H, Sarov-Blat L, O'Brien S, Keiper EA, Johnson AG, Martin J, Goldstein BJ, Shi Y: Human epicardial adipose tissue is a source of inflammatory mediators. Circulation. 2003, 108: 2460-2466. 10.1161/01.CIR.0000099542.57313.C5.View ArticlePubMed
  8. Sacks HS, Fain JN, Cheema P, Bahouth SW, Garrett E, Wolf RY, Wolford D, Samaha J: Depot-specific overexpression of proinflammatory, redox, endothelial cell, and angiogenic genes in epicardial fat adjacent to severe stable coronary atherosclerosis. Metab Syndr Relat Disord. 2011, 9 (6): 433-439. 10.1089/met.2011.0024.View ArticlePubMed
  9. Sturek M, Alloosh M, Wenzel J, Byrd JP, Edwards JM, Lloyd PG, Tune JD, March KL, Miller MA, Mokelke EA, Brisbin IL: Ossabaw Island miniature swine: cardiometabolic syndrome assessment. Swine in the Laboratory: Surgery, Anesthesia, Imaging, and Experimental Techniques. Edited by: Swindle MM. 2007, Boca Raton: CRC Press, 397-402. 2View Article
  10. Edwards JM, Neeb ZP, Alloosh MA, Long X, Bratz IN, Peller CR, Byrd JP, Kumar S, Obukhov AG, Sturek M: Exercise training decreases store-operated Ca2+ entry associated with metabolic syndrome and coronary atherosclerosis. Cardiovasc Res. 2010, 85: 631-640. 10.1093/cvr/cvp308.View ArticlePubMed
  11. Payne GA, Borbouse L, Kumar S, Neeb Z, Alloosh M, Sturek M, Tune JD: Epicardial perivascular adipose-derived leptin exacerbates coronary endothelial dysfunction in metabolic syndrome via a protein kinase C-β pathway. Arterioscler Thromb Vasc Biol. 2010, 30: 1711-1717. 10.1161/ATVBAHA.110.210070.View ArticlePubMedPubMed Central
  12. Neeb ZP, Edwards JM, Alloosh MA, Long X, Mokelke EA, Sturek M: Metabolic syndrome and coronary artery disease in Ossabaw compared with Yucatan swine. Comp Med. 2010, 60: 300-315.PubMedPubMed Central
  13. Sacks HS, Fain JN: Human epicardial fat: what is new and what is missing?. Clin Exp Pharmacol Physiol. 2011, 38: 879-887. 10.1111/j.1440-1681.2011.05601.x.View ArticlePubMed
  14. Institute for Laboratory Animal Research: Guide for the care and use of laboratory animals. 2010, Washington, D.C.: National Academy Press, 8
  15. AVMA Panel on Euthanasia: American veterinary medical association: 2000 report of the AVMA panel on euthanasia. JAVMA. 2001, 218: 669-696.View Article
  16. Arce-Esquivel AA, Kreutzer KV, Rush JW, Turk JR, Laughlin MH: Exercise does not attenuate early CAD progression in a pig model. Med Sci Sports Exerc. 2012, 44: 27-38. 10.1249/MSS.0b013e318228879b.View ArticlePubMedPubMed Central
  17. Bustin SA: Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays. J Mol Endocrinol. 2000, 25: 169-193. 10.1677/jme.0.0250169.View ArticlePubMed
  18. Greif M, Becker A, von Ziegler F, Lebherz C, Lehrke M, Broedl UC, Tittus J, Parhofer K, Becker C, Reiser M, Knez A, Leber AW: Pericardial adipose tissue determined by dual source CT is a risk factor for coronary atherosclerosis. Arterioscler Thromb Vasc Biol. 2009, 29: 781-786. 10.1161/ATVBAHA.108.180653.View ArticlePubMed
  19. Sacks HS, Fain JN: Human epicardial adipose tissue: a review. Am Heart J. 2007, 153: 907-917. 10.1016/j.ahj.2007.03.019.View ArticlePubMed
  20. Horton JD, Cohen JC, Hobbs HH: PCSK9: a convertase that coordinates LDL catabolism. J Lipid Res. 2009, 50: S172-S177.View ArticlePubMedPubMed Central
  21. Owen MK, Witzmann FA, McKenney ML, Lai X, Berwick ZC, Moberly SP, Alloosh M, Sturek M, Tune JD: Perivascular adipose tissue potentiates contraction of coronary vascular smooth muscle: influence of obesity. Circulation. 2013, 128: 9-18. 10.1161/CIRCULATIONAHA.112.001238.View ArticlePubMedPubMed Central
  22. Philippova M, Suter Y, Toggweiler S, Schoenenberger AW, Joshi MB, Kyriakakis E, Erne P, Resink TJ: T-cadherin is present on endothelial microparticles and is elevated in plasma in early atherosclerosis. Eur Heart J. 2011, 32: 760-771. 10.1093/eurheartj/ehq206.View ArticlePubMed
  23. Takeuchi T, Adachi Y, Ohtsuki Y, Furihata M: Adiponectin receptors, with special focus on the role of the third receptor, T-cadherin, in vascular disease. Med Mol Morphol. 2007, 40: 115-120. 10.1007/s00795-007-0364-9.View ArticlePubMed
  24. Kodama T, Freeman M, Rohrer L, Zabrecky J, Matsudaira P, Krieger M: Type I macrophage scavenger receptor contains alpha-helical and collagen-like coiled coils. Nature. 1990, 343: 531-535. 10.1038/343531a0.View ArticlePubMed
  25. Matsumoto A, Naito M, Itakura H, Ikemoto S, Asaoka H, Hayakawa I, Kanamori H, Aburatani H, Takaku F, Suzuki H: Human macrophage scavenger receptors: primary structure, expression, and localization in atherosclerotic lesions. Proc Natl Acad Sci USA. 1990, 87: 9133-9137. 10.1073/pnas.87.23.9133.View ArticlePubMedPubMed Central
  26. Lee L, Alloosh M, Saxena R, Van Alstine W, Watkins BA, Klaunig JE, Sturek M, Chalasani N: Nutritional model of steatohepatitis and metabolic syndrome in the Ossabaw miniature swine. Hepatology. 2009, 50: 56-67. 10.1002/hep.22904.View ArticlePubMedPubMed Central
  27. Zhu XY, Bentley MD, Chade AR, Ritman EL, Lerman A, Lerman LO: Early changes in coronary artery wall structure detected by microcomputed tomography in experimental hypercholesterolemia. Am J Physiol Heart Circ Physiol. 2007, 293: H1997-H2003. 10.1152/ajpheart.00362.2007.View ArticlePubMed
  28. Damas JK, Smith C, Oie E, Fevang B, Halvorsen B, Waehre T, Boullier A, Breland U, Yndestad A, Ovchinnikova O, Robertson AK, Sandberg WJ, Kjekshus J, Tasken K, Froland SS, Gullestad L, Hansson GK, Quehenberger O, Aukrust P: Enhanced expression of the homeostatic chemokines CCL19 and CCL21 in clinical and experimental atherosclerosis: possible pathogenic role in plaque destabilization. Arterioscler Thromb Vasc Biol. 2007, 27: 614-620. 10.1161/01.ATV.0000255581.38523.7c.View ArticlePubMed
  29. Tanaka R, Miwa Y, Mou K, Tomikawa M, Eguchi N, Urade Y, Takahashi-Yanaga F, Morimoto S, Wake N, Sasaguri T: Knockout of the l-pgds gene aggravates obesity and atherosclerosis in mice. Biochem Biophys Res Commun. 2009, 378: 851-856. 10.1016/j.bbrc.2008.11.152.View ArticlePubMed
  30. Dyson M, Alloosh M, Vuchetich JP, Mokelke EA, Sturek M: Components of metabolic syndrome and coronary artery disease in female Ossabaw swine fed excess atherogenic diet. Comp Med. 2006, 56: 35-45.PubMed
  31. Iacobellis G, Singh N, Wharton S, Sharma AM: Substantial changes in epicardial fat thickness after weight loss in severely obese subjects. Obesity (Silver Spring). 2008, 16: 1693-1697. 10.1038/oby.2008.251.View Article
Metadata
Title
Epicardial adipose excision slows the progression of porcine coronary atherosclerosis
Authors
Mikaela L McKenney
Kyle A Schultz
Jack H Boyd
James P Byrd
Mouhamad Alloosh
Shawn D Teague
Arturo A Arce-Esquivel
John N Fain
M Harold Laughlin
Harold S Sacks
Michael Sturek
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Cardiothoracic Surgery / Issue 1/2014
Electronic ISSN: 1749-8090
DOI
https://doi.org/10.1186/1749-8090-9-2

Other articles of this Issue 1/2014

Journal of Cardiothoracic Surgery 1/2014 Go to the issue

Research article

Diagnostic accuracy of tumor necrosis factor-alpha, interferon-gamma, interlukine-10 and adenosine deaminase 2 in differential diagnosis between tuberculous pleural effusion and malignant pleural effusion

Case report

Sutureless management of left ventricle wall rupture; a series of three cases

Review

Airway trauma: a review on epidemiology, mechanisms of injury, diagnosis and treatment

Research article

Blood stasis may cause thrombosis in the left superior pulmonary vein stump after left upper lobectomy

Research article

Left ventricular support adjustment to aortic valve opening with analysis of exercise capacity

Case report

Thoracoscopic surgery for bronchobiliary fistula: a case report