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基因选择的动脉粥样硬化易感性增加的WC-2鸽子的主动脉糖胺聚糖

Aortic glycosaminoglycans in genetically selected WC-2 pigeons with increased atherosclerosis susceptibility.

作者信息

Wagner W D, Nohlgren S R

出版信息

Arteriosclerosis. 1981 May-Jun;1(3):192-201. doi: 10.1161/01.atv.1.3.192.

DOI:10.1161/01.atv.1.3.192
PMID:7295192
Abstract

A genetically selected line of White Carneau pigeons (WC-2) was studied in an attempt to relate changes in composition and content of aortic glycosaminoglycan (GAG) to increased atherosclerosis susceptibility. The WC-2 pigeons were fed an atherogenic diet for 3 months and, when compared to randomly bred White Carneau (RBWC) controls, they showed similar plasma cholesterol concentrations but significantly greater aortic atherosclerosis. In the WC-2 pigeons, 35% of the aortic surface was covered with plaque compared with only 12% in RBWC pigeons; WC-2 birds showed cholesterol contents of 3.3 mg/aorta/500 g body weight, while the RBWC birds had only 0.9 mg/aorta/500 g body weight. After papain treatment of delipidated dried artery, the aortic GAG were isolated, purified using cetylpyridinium chloride, and identified and quantitated by a combination of procedure including selective enzymatic digestion and electrophoresis. In both pigeon groups, aortic GAG included 8% hyaluronic acid, 11% dermatan sulfate, 15% heparan sulfate, and 66% chondroitin sulfate. For the entire group, total aortic GAG content was 35% greater in WC-2 pigeons. Since we did not know if this increase in GAG was simply due to increased atherosclerosis in the WC-2 birds, we sorted the pigeons into matched groups representing minimal, moderate, and severe atherosclerosis on the basis of aortic cholesterol content. At all levels of cholesterol, all GAG contents were greater in the aortas of WC-2 pigeons. The accumulation of dermatan sulfate was 30% higher than in RBWC birds in the minimal arteriosclerosis group, 101% higher in the moderate group, and 53% higher in the severe group. Hyaluronic acid tended to decrease as aortic cholesterol contents increased in WC-2 pigeons. Reduced hyaluronic acid and increase dermatan sulfate may suggest the presence of an altered hyaluronic acid-dermatan sulfate-containing proteoglycan aggregate in the intercellular matrix of the WC-2 pigeon aorta. Possible consequences include increased artery permeability and a binding and retention of lipoproteins in the artery wall. These factors may explain why atherosclerosis develops at an increased rate in the WC-2 pigeon.

摘要

对经过基因筛选的白卡诺鸽品系(WC - 2)进行了研究,旨在探讨主动脉糖胺聚糖(GAG)的组成和含量变化与动脉粥样硬化易感性增加之间的关系。给WC - 2鸽喂食致动脉粥样化饮食3个月,与随机繁殖的白卡诺(RBWC)对照鸽相比,它们的血浆胆固醇浓度相似,但主动脉粥样硬化程度明显更高。在WC - 2鸽中,主动脉表面35%被斑块覆盖,而RBWC鸽仅为12%;WC - 2鸽的主动脉胆固醇含量为3.3毫克/主动脉/500克体重,而RBWC鸽仅为0.9毫克/主动脉/500克体重。用木瓜蛋白酶处理脱脂干燥动脉后,分离主动脉GAG,用十六烷基吡啶氯化物纯化,并通过包括选择性酶消化和电泳在内的一系列方法进行鉴定和定量。在两个鸽组中,主动脉GAG均包括8%的透明质酸、11%的硫酸皮肤素、15%的硫酸乙酰肝素和66%的硫酸软骨素。对于整个组,WC - 2鸽的主动脉GAG总含量高出35%。由于我们不知道GAG的这种增加是否仅仅是由于WC - 2鸽动脉粥样硬化增加所致,我们根据主动脉胆固醇含量将鸽分为代表轻度、中度和重度动脉粥样硬化的匹配组。在所有胆固醇水平下,WC - 2鸽主动脉中的所有GAG含量均更高。在轻度动脉粥样硬化组中,硫酸皮肤素的积累比RBWC鸽高30%,在中度组中高101%,在重度组中高53%。在WC - 2鸽中,随着主动脉胆固醇含量的增加,透明质酸趋于减少。透明质酸减少和硫酸皮肤素增加可能表明WC - 2鸽主动脉细胞间基质中含透明质酸 - 硫酸皮肤素的蛋白聚糖聚集体发生了改变。可能的后果包括动脉通透性增加以及脂蛋白在动脉壁中的结合和滞留。这些因素可能解释了为什么WC - 2鸽的动脉粥样硬化发展速度加快。

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引用本文的文献

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Delayed catabolism of apoB-48 lipoproteins due to decreased heparan sulfate proteoglycan production in diabetic mice.糖尿病小鼠中硫酸乙酰肝素蛋白聚糖生成减少导致载脂蛋白B-48脂蛋白分解代谢延迟。
J Clin Invest. 2000 Jun;105(12):1807-18. doi: 10.1172/JCI8283.
2
Age-related and site-specific adaptation of the arterial endothelial cytoskeleton during atherogenesis.动脉粥样硬化形成过程中动脉内皮细胞骨架的年龄相关性和部位特异性适应性变化
Am J Pathol. 1988 Mar;130(3):595-604.
3
Immunolocalization of proteoglycan types in aortas of pigeons with spontaneous or diet-induced atherosclerosis.
自发性或饮食诱导性动脉粥样硬化鸽子主动脉中蛋白聚糖类型的免疫定位
Am J Pathol. 1989 Mar;134(3):615-26.
4
Macrophage secretory products selectively stimulate dermatan sulfate proteoglycan production in cultured arterial smooth muscle cells.巨噬细胞分泌产物可选择性刺激培养的动脉平滑肌细胞中硫酸皮肤素蛋白聚糖的产生。
Am J Pathol. 1990 Mar;136(3):609-21.