Epicardial adipose excision slows the progression of porcine coronary atherosclerosis

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.

Epicardial adipose tissue: at the heart of the obesity complications

“…The direct involvement of EAT in CAD pathogenesis is also sustained by the evidence that intramyocardial segments of coronary arteries, which are, therefore, not in contact with EAT, are not affected by atherosclerosis [39] and that the selective surgical excision of the portion of EAT covering the coronary artery of a pig model of CAD attenuated the underlying plaque progression in vivo [40].…”

Epicardial Adipose Tissue Volume and Left Ventricular Myocardial Function Using 3-Dimensional Speckle Tracking Echocardiography

“…Embryologically and biochemically different from paracardial mediastinal fat (defined as adipose tissue external to the pericardium), EAT is associated with coronary artery disease (CAD), lipotoxic cardiomyopathy and atrial fibrillation. [1][2][3][4][5][6][7] As a metabolically active organ that releases cytokines and adipokines into the coronary arteries and myocardium [1][2][3][4][5] , EAT may directly alter myocardial contractile function independent of CAD. A recent in-vitro study demonstrated that EAT explanted from guinea pigs secrete factors that inhibit cardiomyocyte contractile function and induce insulin resistance.…”

An Important Question That Needs to Be Proved: Is There Any Relationship between the Epicardial Fat Thickness and the Coronary Artery Complexity in Patients with Acute Non-ST Elevation Myocardial Infarction?

“…In that study, EFT was correlated with the angiographic severity of ACS, but was not correlated with the clinical outcome. It has been reported that the selective surgical excision of adipose tissue in direct contiguity with an epicardial coronary artery attenuated the progression of atherosclerosis in pigs (36). According to these results, it may be hypothesized that factors generated by the epicardial adipose tissue could contribute toward atherogenesis by direct diffusion through adventitia into the coronary intima-media and might locally contribute to stenosis progression.…”