Arterial endothelial function in a porcine model of early stage atherosclerotic vascular disease

Arterial endothelial function in a porcine model of early stage atherosclerotic vascular disease
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DOI:
10.1111/j.0959-9673.2005.00446.x
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发表时间:
2005-10-01
影响因子:
3
通讯作者:
Laughlin, MH
Laughlin, MH
中科院分区:
医学4区
文献类型:
--
作者:
Turk, JR;Henderson, KK;Laughlin, MH

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心血管疾病(CVD)是美国发病率和死亡率的主要原因,预计将成为世界上死亡率的主要原因。动脉粥样硬化是造成这种疾病负担的最重要的单一因素。在这项研究中,我们在饮食诱导的早期动脉粥样硬化性血管疾病动物模型中描述了内皮功能障碍与血管疾病之间的关系。我们验证了高胆固醇血症诱导血管疾病并损害成年雄性尤卡坦猪导管动脉内皮依赖性松弛(EDR)的假设。分别饲喂正常脂肪(NF)或高脂肪胆固醇(HFC)饲粮20-24周。结果表明,虽然HFC饮食没有改变股动脉或肱动脉的EDR,但颈动脉和冠状动脉的EDR均显著降低。腹主动脉和颈总动脉内可见明显的亲苏丹性脂肪条纹。组织病理学检查显示腹主动脉、颈总动脉和股动脉I-III期病变的内膜-中膜厚度(IMT)增加,泡沫细胞积聚。在冠状动脉中,泡沫细胞的积累导致I期和II期病变的IMT增加的趋势。没有证据表明肱动脉有血管疾病。这些结果表明,HFC饮食诱导的早期CVD (Stary I-III期)EDR下降,因为股动脉表现出泡沫细胞积聚和IMT增加,但内皮功能没有改变。
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States and is projected to become the leading cause of mortality in the world. Atherosclerosis is the most important single factor contributing to this disease burden. In this study, we characterize relationships between endothelial dysfunction and vascular disease in an animal model of diet-induced, early-stage atherosclerotic vascular disease. We tested the hypothesis that hypercholesterolaemia induces vascular disease and impairs endothelium-dependent relaxation (EDR) in conduit arteries of adult male Yucatan pigs. Pigs were fed a normal fat (NF) or high fat cholesterol (HFC) diet for 20-24 weeks. Results indicate that, while the HFC diet did not alter EDR in femoral or brachial arteries, EDR was significantly decreased in both carotid and coronary arteries. Sudanophilic fatty streaks were significantly present in the abdominal aorta and common carotid artery. Histopathology revealed increased intima-media thickness (IMT) and foam cell accumulation in Stary Stage I-III lesions in the abdominal aorta, common carotid artery and femoral arteries. In the coronary arteries, the accumulation of foam cells in Stary Stage I and II lesions resulted in a trend for increased IMT. There was no evidence of vascular disease in the brachial arteries. These results indicate that early stages of CVD (Stary Stage I-III) precede decreases in EDR induced by HFC diet, because femoral arteries exhibited foam cell accumulation and an increased IMT but no change in endothelial function.