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Browsing by Author "Bruning, Rebecca S."
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Item Effect of metabolic syndrome and aging on Ca2+ dysfunction in coronary smooth muscle and coronary artery disease severity in Ossabaw miniature swine(Elsevier, 2018-07-15) Badin, Jill K.; Bruning, Rebecca S.; Sturek, Michael; Cellular and Integrative Physiology, School of MedicineBACKGROUND: Metabolic syndrome (MetS) and aging are prevalent risk factors for coronary artery disease (CAD) and contribute to the etiology of CAD, including dysregulation of Ca2+ handling mechanisms in coronary smooth muscle (CSM). The current study tested the hypothesis that CAD severity and CSM Ca2+ dysregulation were different in MetS-induced CAD compared to aging-induced CAD. METHODS: Young (2.5 ± 0.2 years) and old (8.8 ± 1.2 years) Ossabaw miniature swine were fed an atherogenic diet for 11 months to induce MetS and were compared to lean age-matched controls. The metabolic profile was confirmed by body weight, plasma cholesterol and triglycerides, and intravenous glucose tolerance test. CAD was measured with intravascular ultrasound and histology. Intracellular Ca2+ ([Ca2+]i) was assessed with fura-2 imaging. RESULTS: CAD severity was similar between MetS young and lean old swine, with MetS old swine exhibiting the most severe CAD. Compared to CSM [Ca2+]i handling in lean young, the MetS young and lean old swine exhibited increased sarcoplasmic reticulum Ca2+ store release, increased Ca2+ influx through voltage-gated Ca2+ channels, and attenuated sarco-endoplasmic reticulum Ca2+ ATPase activity. MetS old and MetS young swine had similar Ca2+ dysregulation. CONCLUSIONS: Ca2+ dysregulation, mainly the SR Ca2+ store, in CSM is more pronounced in lean old swine, which is indicative of mild, proliferative CAD. MetS old and MetS young swine exhibit Ca2+ dysfunction that is typical of late, severe disease. The more advanced, complex plaques in MetS old swine suggest that the "aging milieu" potentiates effects of Ca2+ handling dysfunction in CAD.Item Epicardial Adipose Tissue Removal Potentiates Outward Remodeling and Arrests Coronary Atherogenesis(Elsevier, 2017-05) McKenney-Drake, Mikaela L.; Rodenbeck, Stacey D.; Bruning, Rebecca S.; Kole, Ayeeshik; Yancey, Kyle W.; Alloosh, Mouhamad; Sacks, Harold S.; Sturek, Michael; Cellular and Integrative Physiology, School of MedicineBACKGROUND: Pericoronary 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. Although 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 randomly allocated into sham (n = 5) or adipectomy (n = 7) groups. Both groups underwent a thoracotomy, opening of the pericardial sac, and placement of radioopaque clips to mark the proximal left anterior descending artery. Adipectomy swine underwent removal of 1 to 1.5 cm2 of cEAT from the proximal artery. After sham or adipectomy, CAD severity was assessed with intravascular ultrasonography. Swine recovered for an additional 3 months on an atherogenic diet, and CAD was assessed immediately before euthanasia. Artery sections were processed for histologic and immunohistochemical analysis. RESULTS: Severity of CAD as assessed by percent stenosis was reduced in the adipectomy cohort compared with shams; however, plaque size remained unaltered, whereas larger plaque sizes developed in sham-operated swine. 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.Item High-speed intravascular photoacoustic imaging at 1.7 μm with a KTP-based OPO(The Optical Society, 2015-11-01) Hui, Jie; Yu, Qianhuan; Ma, Teng; Wang, Pu; Cao, Yingchun; Bruning, Rebecca S.; Qu, Yueqiao; Chen, Zhongping; Zhou, Qifa; Sturek, Michael; Cheng, Ji-Xin; Chen, Weibiao; Department of Cellular & Integrative Physiology, IU School of MedicineLipid deposition inside the arterial wall is a hallmark of plaque vulnerability. Based on overtone absorption of C-H bonds, intravascular photoacoustic (IVPA) catheter is a promising technology for quantifying the amount of lipid and its spatial distribution inside the arterial wall. Thus far, the clinical translation of IVPA technology is limited by its slow imaging speed due to lack of a high-pulse-energy high-repetition-rate laser source for lipid-specific first overtone excitation at 1.7 μm. Here, we demonstrate a potassium titanyl phosphate (KTP)-based optical parametric oscillator with output pulse energy up to 2 mJ at a wavelength of 1724 nm and with a repetition rate of 500 Hz. Using this laser and a ring-shape transducer, IVPA imaging at speed of 1 frame per sec was demonstrated. Performance of the IVPA imaging system's resolution, sensitivity, and specificity were characterized by carbon fiber and a lipid-mimicking phantom. The clinical utility of this technology was further evaluated ex vivo in an excised atherosclerotic human femoral artery with comparison to histology.