Genes, endothelial function and cerebral small vessel disease in man
Genes, endothelial function and cerebral small vessel disease in man
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DOI：
10.1113/expphysiol.2007.038752
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发表时间：
2008-01-01
影响因子：
2.7
通讯作者：
Markus, Hugh S.
中科院分区：
文献类型：
--
作者：
Markus, Hugh S.
脑小血管病是由供应白色物质和深灰质核团的穿通动脉缺血引起的。它导致局灶性腔隙性梗死和更弥漫的慢性缺血区域（脑白质疏松）。可能存在两种亚型。一种亚型（孤立性腔隙性梗死）与单个或少数较大的腔隙性梗死相关，无脑白质疏松，可能由较大的穿通动脉中的微粥样硬化引起。第二种亚型（缺血性脑白质疏松症）导致多发性小腔隙性梗死，继发于影响较小穿通动脉的弥漫性动脉病的脑白质疏松症，通常发生在高血压的情况下。在这种亚型中，已报告慢性灌注不足和脑自动调节受损。许多证据支持内皮激活和功能障碍的致病作用。遗传易感性也有牵连。与内皮功能相关的基因，包括调节肾素-血管紧张素系统、内皮一氧化氮和同型半胱氨酸水平的基因，已经有报道。然而，并不是所有的结果都被复制，几乎没有强大的可复制的关联。需要更大规模的研究来确定哪些关联代表重要的风险因素。
Cerebral small vessel disease results from ischaemia in the perforating arteries supplying the white matter and deep grey matter nuclei. It results in both focal lacunar infarction and more diffuse areas of chronic ischaemia (leukoaraiosis). Two subtypes may exist. One subtype (isolated lacunar infarction) is associated with single or a few larger lacunar infarcts without leukoaraiosis, and may result from microatheroma in the larger perforating arteries. The second subtype (ischaemic leukoaraiosis) results in multiple small lacunar infarcts with leukoaraiosis secondary to a diffuse arteriopathy affecting the smaller perforating arteries, usually occurring in the presence of hypertension. In this subtype, chronic hypoperfusion and impaired cerebral autoregulation have been reported. A number of lines of evidence support a pathogenic role of endothelial activation and dysfunction. Genetic predisposition has also been implicated. Associations with genes involved in endothelial function, including those regulating the renin-angiotensin system, endothelial nitric oxide and homocysteine levels, have been reported. However, not all results have been replicated and there are few robust replicable associations. Larger studies are required to determine definitively which associations represent important risk factors.