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Open Access Highly Accessed Research article

Epicardial adipose excision slows the progression of porcine coronary atherosclerosis

Mikaela L McKenney1, Kyle A Schultz1, Jack H Boyd2, James P Byrd1, Mouhamad Alloosh1, Shawn D Teague3, Arturo A Arce-Esquivel4, John N Fain5, M Harold Laughlin4, Harold S Sacks67 and Michael Sturek1*

  • * Corresponding author: Michael Sturek msturek@iu.edu

  • † Equal contributors

Author Affiliations

1 Departments of Cellular & Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, Room 385, Indianapolis, IN 46202-5120, USA

2 Department of Cardiothoracic Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA

3 Department of Radiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA

4 Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA

5 Department of Molecular Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA

6 Endocrinology and Diabetes Division, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA

7 David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA

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Journal of Cardiothoracic Surgery 2014, 9:2  doi:10.1186/1749-8090-9-2

Published: 3 January 2014

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.

Keywords:
Atherosclerosis; Computed tomography; Surgery; Intravascular ultrasound