Decreased coronary vascular reserve in Watanabe heritable hyperlipidemic rabbits.

Clozel, Jean‐Paul; Lengsfeld, Hans; Kühn, Herbert; Baumgartner, Hans R.

doi:10.1161/01.atv.8.3.310

Cited by 16 publications

(4 citation statements)

References 20 publications

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“…In the present study, we examined the atherosclerotic lesions of the left circumflex arteries (LCXs). The LCXs of rabbits have a greater diameter and length than those of the left anterior descending artery [4], and atherosclerotic lesions develop more frequently in the LCX than in the left anterior descending artery in WHHLMI rabbits [11, 22, 24]. …”

Section: Methodsmentioning

confidence: 99%

Morphological features of coronary plaques in WHHLMI rabbits (<i>Oryctolagus cuniculus</i>), an animal model for familial hypercholesterolemia

et al. 2017

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Abstract:In order to examine their suitability for studies on coronary atherosclerosis, we evaluated the features of coronary atherosclerotic plaques in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits, a spontaneous animal model for coronary atherosclerosis and myocardial infarction. Coronary segments of the hearts of 187 WHHLMI rabbits (10-29 months old) were sectioned serially and stained histopathologically and immunohistologically. Progression of coronary lesions was prominent in rabbits that had died suddenly. The degree of coronary lesions of females was higher than that of males. Various types of atherosclerotic lesions were observed in the coronary arteries, such as plaques with a large lipid core covered by a thin fibrous cap, fatty streaks, early and advanced fibroatheromas, fibrous lesions, and advanced lesions with calcium accumulation and the vasa vasorum. In rabbits that had died suddenly, the frequencies of fibroatheromas or advanced lesions were higher than those of rabbits euthanized. Matrix metalloproteinase (MMP)-positive macrophages were detected in gaps among endothelial cells at the plaque surface, beneath the fibrous cap of thin-capped fibroatheromas, and at the bottom of the intimal plaques in which the tunica media was attenuated. Immunohistological results suggest that MMP-positive macrophages are involved in the initiation, progression, and destabilization of coronary plaques, in addition to vascular remodeling, even in WHHLMI rabbits. In conclusion, coronary lesions in WHHLMI rabbits resemble human atherosclerotic lesions, and thus, the WHHLMI rabbit is a suitable animal model for studies on human coronary plaques.

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Section: Methodsmentioning

confidence: 99%

Morphological features of coronary plaques in WHHLMI rabbits (<i>Oryctolagus cuniculus</i>), an animal model for familial hypercholesterolemia

et al. 2017

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“…Hypercholesterolemia induces microvascular dysfunction characterized by loss of endotheliumderived nitric oxide, increased rolling and adherence of leukocytes, and increased expression of P-selectin (10). Hypercholesterolemia also impairs coronary and aortic endothelium-dependent relaxation (EDR) in humans (5,24) and animal models (3,20,32). Previous studies showed that infarct size after coronary occlusionreperfusion is significantly larger in animals with acute or chronic hypercholesterolemia than in normal animals (11,15,18).…”

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confidence: 99%

Cholesterol feeding exacerbates myocardial injury in Zucker diabetic fatty rats

Hoshida

Yamashita

Otsu

et al. 2000

American Journal of Physiology-Heart and Circulatory Physiology

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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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“…Blood pressure was also monitored invasively at the femoral artery.. We analyzed the left circumflex artery (LCX) because it is a major coronary artery in rabbits [1, 13], and severe atherosclerotic lesions were observed in LCX; however, the degree of lesions was shown to markedly vary and the frequency of atherosclerotic lesions was low in the anterior descending artery [14]. …”

Section: Methodsmentioning

confidence: 99%

High susceptibility of atherosclerotic coronary arteries to the onset of vasospasm and angina pectoris-like symptoms due to coronary spasm in WHHLMI rabbits

Koike

Tamura

et al. 2016

Exp. Anim.

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We examined the relationship between atherosclerosis and the provocation of coronary spasm as well as the influence of coronary spasm on the onset of acute ischemic myocardial disease. Coronary spasm was provoked in anesthetized normal Japanese white (JW) rabbits and myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits, an animal model for coronary atherosclerosis and myocardial infarction, by injecting ergonovine during the infusion of norepinephrine through a marginal ear vein. A decrease in contrast flow in the left circumflex artery was observed on coronary angiograms. Ischemic changes were observed on the electrocardiograms of 29% (2/7) of JW and 79% (27/34, P=0.007) of WHHLMI rabbits. The frequency of coronary spasm was significantly high in rabbits with severe coronary plaques showing diffuse lesions. Left ventricle motility in vasospasm-positive rabbits, which was evaluated with echocardiograms, was decreased by 29% following the ergonovine injection (P<0.001), and every serum ischemic marker markedly increased 4 h after the provocation of vasospasm. These results demonstrate that atherosclerotic coronary arteries are positively related to the provocation of vasospasm, and vasospasm in severe atherosclerotic coronary segments evokes angina pectoris-like findings and/or non-fatal myocardial infarction. WHHLMI rabbits may be a novel animal model for angina pectoris and acute ischemic heart disease.

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Decreased coronary vascular reserve in Watanabe heritable hyperlipidemic rabbits.

Cited by 16 publications

References 20 publications

Morphological features of coronary plaques in WHHLMI rabbits (<i>Oryctolagus cuniculus</i>), an animal model for familial hypercholesterolemia

Morphological features of coronary plaques in WHHLMI rabbits (<i>Oryctolagus cuniculus</i>), an animal model for familial hypercholesterolemia

Cholesterol feeding exacerbates myocardial injury in Zucker diabetic fatty rats

High susceptibility of atherosclerotic coronary arteries to the onset of vasospasm and angina pectoris-like symptoms due to coronary spasm in WHHLMI rabbits

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