Epicardial adipose excision slows the progression of porcine coronary atherosclerosis

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

doi:10.1186/1749-8090-9-2

Abstract

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

Highlights

In humans there is a positive association between epicardial adipose tissue (EAT) volume and coronary atherosclerosis (CAD) burden
Metabolic characteristics At adipectomy, pigs on the atherogenic diet had developed coronary artery disease (CAD) and its risk factors including hypertension, obesity, increased LDL/HDL ratio, insulin resistance, glucose intolerance and increased triglyceride levels compared to age-matched lean controls (Table 2)
There was no difference between baseline mean proximal and middle left anterior descending artery (LAD) plaque lengths (p = 0.26), whereas middle LAD was higher than distal LAD (p = 0.01) and proximal was greater than distal (p = 0.04)

Summary

Introduction

In humans there is a positive association between epicardial adipose tissue (EAT) volume and coronary atherosclerosis (CAD) burden. EAT volume expansion in CAD occurs independently of associated increases in visceral abdominal and total body fat mass as well as changes in other CAD risk factors [2,3]. This epidemiological evidence together with pathophysiological data showing increased chronic inflammatory cell infiltrates [7] and up-regulation of pro-inflammatory, redox, macrophage marker, and angiogenic gene expression in EAT sampled from humans undergoing coronary artery bypass for severe CAD [8] is the basis for the hypothesis that EAT might contribute locally and detrimentally to coronary atherogenesis. To our knowledge, there is no direct experimental evidence that EAT plays a role in coronary atherogenesis

Methods

Results

Discussion

Conclusion