Epicardial Adipose Tissue Removal Potentiates Outward Remodeling and Arrests Coronary Atherogenesis

Abstract

Background Peri-coronary 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. While 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 randomized into sham (n=5) or adipectomy (n=7) groups. Both groups underwent a thoracotomy, opening of the pericardial sac, and placement of radio-opaque clips to mark the proximal left anterior descending artery. Adipectomy swine underwent removal of 1–1.5 cm2 of cEAT from the proximal artery. Following sham or adipectomy, CAD severity was assessed with intravascular ultrasound. Swine recovered for an additional 3 months on atherogenic diet and CAD was assessed immediately prior to euthanasia. Artery sections were processed for histological and immunohistochemical analysis. Results CAD severity, as assessed by percent stenosis, was reduced in the adipectomy cohort compared to shams; however, plaque size remained unaltered, while sham-operated swine developed greater plaque sizes. 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.

The epicardial adipose inflammatory triad: coronary atherosclerosis, atrial fibrillation, and heart failure with a preserved ejection fraction

“…Focal obstructive lesions reside in the coronary arterial segments that are immediately adjacent to areas of epicardial fat with the greatest thickness, 3 and experimental resection of the epicardium ameliorates coronary atherosclerosis. 4 These observations support the hypothesis that the accumulation of epicardial adipose tissue (and inflammation of perivascular fat) can act in a paracrine manner to adversely influence the structure and function of the coronary arteries.…”

“…In chronic inflammatory states, the accumulation of epicardial adipose tissue is closely associated with the presence, severity and progression of coronary artery disease, in a manner that is independent of circulating lipids or adiposity. Focal obstructive lesions reside in the coronary arterial segments that are immediately adjacent to areas of epicardial fat with the greatest thickness, and experimental resection of the epicardium ameliorates coronary atherosclerosis . These observations support the hypothesis that the accumulation of epicardial adipose tissue (and inflammation of perivascular fat) can act in a paracrine manner to adversely influence the structure and function of the coronary arteries.…”

Simple and reproducible approaches for the collection of select porcine ganglia

“…In recent years, their use in translational research has significantly expanded due to the development of genetically modified and experimentally-induced pig models of human disease. These include cystic fibrosis 19–21 , muscular dystrophy 22 , diabetes 23 , cardiovascular disease 24,2526 , diabetes 27 , cancer 28,29 , environmental toxicology 30 , cutaneous wound healing 31 , metabolic syndrome 32 , among others. Porcine models have also been used to investigate traumatic brain injury 3 , neurodegenerative diseases 33,34 , brain development 35 , seizures 36 , cognition 37 , and neurogenesis 38 .…”

Relationship between epicardial and perivascular fatty tissue and adipokine-cytokine level in coronary artery disease patients

“…However, against the background of obesity and the progression of coronary atherosclerosis, the phenotype of EAT adipocytes from brown to white changes due to activation of the IL-6 signaling pathway of JAK-STAT3 [26]. For white PVAT adipocytes, obesity is characterized by intense lipolysis with the formation of FFA, as well as an increase in the production of pro-inflammatory factors (IL-1β, IL-6, TNF-α) and leptin, which enters the bloodstream and causes irreversible changes in the body (i.e., dyslipidemia and insulin resistance).…”

“…Perivascular fat is located around vessels of different sizes, does not have barriers separating it from the adventitia of the vessel [26], therefore, this results in synthesized cytokines and chemokines can act directly on the vascular wall, potentiating vasospasm, endothelial dysfunction, proliferation of smooth muscle cells, migration of leukocytes in the intima, and fibrosis [27]. A large amount of data supports regional, phenotypic, and functional differences between deposits of different localizations [28].…”