Cholesterol feeding exacerbates myocardial injury in Zucker diabetic fatty rats
Abstract
We measured infarct size after coronary occlusion (30 min) and reperfusion (24 h) in genetic non-insulin-dependent Zucker diabetic fatty (ZDF) rats with and without 4-wk cholesterol feeding. Infarct size was similar in ZDF rats and lean control rats but was significantly larger in cholesterol-fed diabetic rats than in cholesterol-fed lean rats ( P < 0.05). Plasma levels of glucose, insulin, and triglycerides were significantly higher in diabetic rats and were not influenced by cholesterol feeding. The increase in total plasma cholesterol induced by cholesterol feeding was significantly greater in diabetic rats than in lean rats ( P < 0.05). A significant positive correlation was found between total plasma cholesterol and infarct size ( P < 0.05). Myeloperoxidase activity, as an index of neutrophil accumulation, was significantly higher and expression of P-selectin was more marked in the ischemic myocardium of cholesterol-fed diabetic rats than of cholesterol-fed lean rats. Acetylcholine-induced endothelium-dependent relaxation (EDR) of aortic rings was markedly impaired in cholesterol-fed diabetic rats. Thus cholesterol feeding significantly exacerbated myocardial injury produced by coronary occlusion-reperfusion in non-insulin-dependent diabetic rats, possibly because of enhanced expression of P-selectin and impairment of EDR in the coronary bed.
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Studies performed in vivo using coronary artery ligation show that obesity and insulin resistance are associated with impaired recovery of cardiac function in genetic models such as Zucker rats, db/db mice, and mice with diet-induced obesity.
“Studies performed in vivo using coronary artery ligation show that obesity and insulin resistance are associated with impaired recovery of cardiac function. This is true in genetic models such as Zucker rats, db/db mice, and mice with diet-induced obesity (119, 146, 346).”
From Cardiac remodeling in obesity (2008) · cites this paper as [146]
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- Authors
- Hoshida, S., Yamashita, N., Otsu, K., Kuzuya, T., & Hori, M.
- Affiliations
- Osaka Rosai Hospital (JP)
- The University of Osaka (JP)
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2000-01-01
- Volume
- 278
- Issue
- 1
- Pages
- H256-H262
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- OpenAlex
- W2100518671
- Cited by
- 40
- References
- 40
- Citations by year
- 2025: 2 · 2023: 1 · 2022: 1 · 2020: 2 · 2019: 1 · 2017: 2 · 2016: 1 · 2013: 5 · 2012: 1
- FWCI
- 0.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Keywords
- cholesterol feeding, myocardial infarct size, Zucker diabetic fatty rats, type 2 diabetes, serum cholesterol, P-selectin, myeloperoxidase, neutrophil accumulation, endothelium-dependent relaxation, acetylcholine, endothelial dysfunction, hypertriglyceridemia
- MeSH terms
- Acetylcholine, Animals, Aorta, Cholesterol, Dietary, Diabetes Mellitus, Diabetes Mellitus, Type 2, Endothelium, Vascular, Hemodynamics, Male, Peroxidase, Myocardial Infarction, Myocardium, Neutrophils, Obesity, Rats, Zucker, Vasodilation, Vasodilator Agents, Cell Adhesion Molecules, Rats, In Vitro Techniques
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