期刊
ATHEROSCLEROSIS
卷 249, 期 -, 页码 1-9出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2016.03.032
关键词
Calcium regulation; Smooth muscle phenotype; Proliferation; Ossabaw swine
资金
- National Institutes of Health [HL062552, T32 DK064466]
- American Heart Association [15PRE25280001]
- Indiana CTSI Predoctoral TL1 Training Fellowship [TR000162]
- Fortune-Fry Ultrasound Research Fund
- Cardiometabolic Disease Research Foundation
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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据