期刊
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
卷 15, 期 1, 页码 167-178出版社
SPRINGER
DOI: 10.1007/s12265-021-10153-5
关键词
Atherosclerosis; Obesity; Metabolic syndrome; Histology; Sarco-endoplasmic reticulum Ca2+ ATPase; Ca2+ influx; Ca2+ release; Animal model; Risk factors
资金
- National Institutes of Health [HL125385, P30 DK097512]
- Joshua Diabetes Research Fund
- Indiana University School of Medicine Center of Excellence in Cardiovascular Research
In coronary smooth muscle of atherosclerotic coronary artery disease in metabolic syndrome swine, intracellular free Ca2+ dysregulation occurs. Increased [Ca2+](i) signaling in human CAD is associated with advanced age and a greater media area, while decreased signaling is related to a higher number of risk factors and plaque burden in human and swine CAD. Similar [Ca2+](i) dysregulation in human and Ossabaw swine CSM supports the translational relevance of this large animal model.
Intracellular free Ca2+ ([Ca2+](i)) 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 [Ca2+](i) 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 [Ca2+](i) elicited by Ca2+ influx and sarcoplasmic reticulum (SR) Ca2+ release and sequestration was measured with fura-2. Increased [Ca2+](i) signaling was associated with advanced age and a greater media area in human CAD. Decreased [Ca2+](i) signaling was associated with a greater number of risk factors and a higher plaque burden in human and swine CAD. Similar [Ca2+](i) dysregulation exhibited in human and Ossabaw swine CSM provides strong evidence for the translational relevance of this large animal model.
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