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.

With progressive CKD in the Cy/+ rat there is increased resting [Ca 2+ ] i in VSMCs due, in part, to increased SOCE and impaired calcium extrusion from the cell. Such changes may predispose VSMCs to phenotypic changes that are a prerequisite to calcification.

Background and Aims Coronary artery disease (CAD) is progressive, classified by stages of severity. Alterations in Ca2+ regulation within coronary smooth muscle (CSM) cells in metabolic syndrome (MetS) have been observed, but there is a lack of data in relatively early (mild) and late (severe) stages of CAD. The current study examined alterations in CSM Ca2+ regulation at several time points during CAD progression. Methods MetS was induced by feeding an excess calorie atherogenic diet for 6, 9, or 12 months and compared to age-matched lean controls. CAD was measured with intravascular ultrasound (IVUS). Intracellular Ca2+ was assessed with fura-2. Results IVUS revealed that the extent of atherosclerotic CAD correlated with the duration on atherogenic diet. Fura-2 imaging of intracellular Ca2+ in CSM cells revealed heightened Ca2+ signaling at 9 months on diet, compared to 6 and 12 months, and to age-matched lean controls. Isolated coronary artery rings from swine fed for 9 months followed the same pattern, developing greater tension to depolarization, compared to 6 and 12 months (6 months= 1.8±0.6 g, 9 months= 5.0±1.0 g, 12 months= 0.7±0.1 g). CSM in severe atherosclerotic plaques showed dampened Ca2+ regulation and decreased proliferation compared to CSM from the wall. Conclusions These CSM Ca2+ regulation data from several time points in CAD progression and severity help to resolve the controversy regarding up- vs. down-regulation of CSM Ca2+ regulation in previous reports. These data are consistent with the hypothesis that alterations in sarcoplasmic reticulum Ca2+ contribute to progression of atherosclerotic CAD in MetS.

Ossabaw miniature swine were fed an excess calorie, atherogenic diet for 6, 9, or 12 months. Increased body weight, hypertension, and increased plasma cholesterol and triglycerides are described in Table 1. For more detailed interpretations and conclusions about the data, see our associated research study, “Biphasic alterations in coronary smooth muscle Ca2+ regulation during coronary artery disease progression in metabolic syndrome” McKenney-Drake, et al. (2016) [1].

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