纯合子型同型胱氨酸尿症患儿的体循环动脉存在内皮功能受损的情况，但其杂合子型父母却没有。

Impaired endothelial function occurs in the systemic arteries of children with homozygous homocystinuria but not in their heterozygous parents.

作者信息

Celermajer D S, Sorensen K, Ryalls M, Robinson J, Thomas O, Leonard J V, Deanfield J E

机构信息

Cardiothoracic Unit, Hospital for Sick Children, London, England, United Kingdom.

出版信息

J Am Coll Cardiol. 1993 Sep;22(3):854-8. doi: 10.1016/0735-1097(93)90203-d.

DOI:10.1016/0735-1097(93)90203-d

PMID:8354824

Abstract

OBJECTIVES

Because endothelial dysfunction is an early event in atherogenesis, we aimed to determine whether endothelial function is normal or impaired in the systemic arteries of children with homozygous homocystinuria or in those of heterozygous adults, or both.

BACKGROUND

Homocystinuria is strongly associated with premature vascular disease in homozygotes, and even heterozygotes have been shown to be at increased risk from early atherosclerosis associated with hyperhomocystinemia.

METHODS

We conducted noninvasive studies on the superficial femoral or brachial arteries of 9 children aged 4 to 17 years (mean 11) with homozygous homocystinuria and on the brachial arteries of 14 obligate heterozygous parents age 33 to 49 years (mean 41). Each subject was matched with two control subjects. Using high resolution ultrasound, we measured vessel diameter at rest, during reactive hyperemia (with flow increase causing endothelium-dependent dilation) and after sublingual administration of nitroglycerin (an endothelium-independent vasodilator).

RESULTS

Flow-mediated dilation was observed in the control children (9 +/- 0.6%, range 6% to 14%) but was impaired in the children with homocystinuria (2.8 +/- 0.7%, range 0% to 7%, p < 0.0001). In contrast, nitroglycerin-mediated dilation was similar in both groups (15.7 +/- 1.6% vs. 13.1 +/- 1.2%, p = 0.27), indicating that the impaired flow-mediated dilation is secondary to endothelial dysfunction. In the heterozygous parents, both flow-mediated dilation and nitroglycerin responses (6.3 +/- 0.9%, 17 +/- 1.4%, respectively) were similar to control values (6.8 +/- 0.7%, 20.7 +/- 1.7%, p > 0.10).

CONCLUSIONS

Children with homozygous homocystinuria had impaired endothelial function in the systemic arteries as early as 4 years of age, representing an early event in their premature vascular disease. However, endothelial function was preserved in the heterozygous adults.

摘要

目的

由于内皮功能障碍是动脉粥样硬化发生的早期事件，我们旨在确定纯合子型同型胱氨酸尿症患儿或杂合子型成年人或两者的全身动脉内皮功能是否正常或受损。

背景

同型胱氨酸尿症与纯合子过早发生血管疾病密切相关，甚至已表明杂合子因高同型半胱氨酸血症相关的早期动脉粥样硬化而处于风险增加状态。

方法

我们对9名年龄在4至17岁（平均11岁）的纯合子型同型胱氨酸尿症患儿的股浅动脉或肱动脉以及14名年龄在33至49岁（平均41岁）的杂合子型患儿的父母的肱动脉进行了无创研究。每个受试者与两名对照受试者进行匹配。使用高分辨率超声，我们测量了静息时、反应性充血期间（血流增加导致内皮依赖性扩张）以及舌下含服硝酸甘油后（一种非内皮依赖性血管扩张剂）的血管直径。

结果

在对照儿童中观察到血流介导的扩张（9±0.6%，范围6%至14%），但在同型胱氨酸尿症患儿中受损（2.8±0.7%，范围0%至7%，p<0.0001）。相比之下，两组中硝酸甘油介导的扩张相似（15.7±1.6%对13.1±1.2%，p = 0.27），表明血流介导的扩张受损是内皮功能障碍的继发结果。在杂合子型患儿的父母中，血流介导的扩张和硝酸甘油反应（分别为6.3±0.9%，17±1.4%）与对照值相似（6.8±0.7%，20.7±1.7%，p>0.10）。