Abstract | OBJECTIVE: Impaired angiogenesis is a known consequence of metabolic syndrome (MetS); however, the mechanism is not fully understood. Recent studies have shown that the notch signaling pathway is an integral component of cardiac angiogenesis. We tested, in a clinically relevant swine model, the effects of MetS on notch and apoptosis signaling in chronically ischemic myocardium. METHODS: Ossabaw swine were fed either a regular diet (control [CTL], n = 8) or a high- cholesterol diet (MetS, n = 8) to induce MetS. An ameroid constrictor was placed to induce chronic myocardial ischemia. Eleven weeks later, the wine underwent cardiac harvest of the ischemic myocardium. RESULTS: CONCLUSIONS: MetS in chronic myocardial ischemia significantly impairs notch signaling by downregulating notch receptors, ligands, and pro-angiogenesis proteins. MetS also increases apoptosis signaling, decreases survival signaling, and increases cell death in chronically ischemic myocardium. Although short-term angiogenesis appears unaffected in this model of early MetS, the molecular signals for angiogenesis are impaired, suggesting that inhibition of notch signaling might underlie the decreased angiogenesis in later stages of MetS.
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Authors | Nassrene Y Elmadhun, Ashraf A Sabe, Antonio D Lassaletta, Louis M Chu, Katelyn Kondra, Michael Sturek, Frank W Sellke |
Journal | The Journal of thoracic and cardiovascular surgery
(J Thorac Cardiovasc Surg)
Vol. 148
Issue 3
Pg. 1048-55; discussion 1055
(Sep 2014)
ISSN: 1097-685X [Electronic] United States |
PMID | 25037620
(Publication Type: Journal Article)
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Copyright | Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved. |
Chemical References |
- Angiogenic Proteins
- Apoptosis Regulatory Proteins
- Receptors, Notch
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Topics |
- Angiogenic Proteins
(metabolism)
- Animals
- Apoptosis
- Apoptosis Regulatory Proteins
(metabolism)
- Chronic Disease
- Disease Models, Animal
- Male
- Metabolic Syndrome
(complications, metabolism, pathology, physiopathology)
- Myocardial Ischemia
(complications, metabolism, pathology, physiopathology)
- Myocardium
(metabolism, pathology)
- Neovascularization, Physiologic
- Receptors, Notch
(metabolism)
- Signal Transduction
- Swine
- Swine, Miniature
- Time Factors
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