冠状动脉平滑肌细胞内钙调控异常在人类冠心病和奥萨鲍微型猪模型中相似。
Intracellular Ca Dysregulation in Coronary Smooth Muscle Is Similar in Coronary Disease of Humans and Ossabaw Miniature Swine.
机构信息
Department of Anatomy, Cell Biology, & Physiology, Indiana University School of Medicine, 635 Barnhill Dr., Medical Sciences, Room 385, Indianapolis, IN, 46202, USA.
Marian University College of Osteopathic Medicine, Indianapolis, IN, 46222, USA.
出版信息
J Cardiovasc Transl Res. 2022 Feb;15(1):167-178. doi: 10.1007/s12265-021-10153-5. Epub 2021 Jul 20.
Intracellular free Ca ([Ca]) dysregulation occurs in coronary smooth muscle (CSM) in atherosclerotic coronary artery disease (CAD) of metabolic syndrome (MetS) swine. Our goal was to determine how CAD severity, arterial structure, and MetS risk factors associate with [Ca] dysregulation in human CAD compared to changes in Ossabaw miniature swine. CSM cells were dispersed from coronary arteries of explanted hearts from transplant recipients and from lean and MetS swine with CAD. CSM [Ca] elicited by Ca influx and sarcoplasmic reticulum (SR) Ca release and sequestration was measured with fura-2. Increased [Ca] signaling was associated with advanced age and a greater media area in human CAD. Decreased [Ca] signaling was associated with a greater number of risk factors and a higher plaque burden in human and swine CAD. Similar [Ca] dysregulation exhibited in human and Ossabaw swine CSM provides strong evidence for the translational relevance of this large animal model.
细胞内游离钙 ([Ca]) 失调发生在代谢综合征 (MetS) 猪的动脉粥样硬化性冠状动脉疾病 (CAD) 的冠状动脉平滑肌 (CSM) 中。我们的目标是确定 CAD 严重程度、动脉结构和 MetS 风险因素与人类 CAD 中 [Ca] 失调的关联，以及 Ossabaw 小型猪的变化。CSM 细胞从移植受者心脏移植的冠状动脉和患有 CAD 的瘦猪和 MetS 猪中分离出来。用 fura-2 测量钙内流和肌浆网 (SR) 钙释放和摄取引起的 CSM [Ca]。在人类 CAD 中，较高的 [Ca] 信号与年龄较大和中膜面积较大有关。在人类和 Ossabaw 猪 CAD 中，[Ca] 信号降低与更多的危险因素和更高的斑块负担有关。人类和 Ossabaw 猪 CSM 中出现的类似 [Ca] 失调为这种大型动物模型的转化相关性提供了有力证据。
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