Studies of Vascular Related Genes in Rodent Stroke Model
Date Issued
2007
Date
2007
Author(s)
Lai, Dar-Ming
DOI
zh-TW
Abstract
Angiopoietin-like protein (Angptl) 1, a member of the angiopoietin-related protein family, modulates angiogenesis but little else is known of its physiological role. We found that angptl1 was upregulated at the 7th day after focal cerebral ischemia in normal mice. In order to understand the role of angptl1 in cerebral infarction, we induced focal cerebral ischemia in normal and glial fibrillary acidic protein promoter-angptl1 transgenic mice. In the transgenic mice without ischemia, overexpression of angptl1 in the whole brain led to a decrease in cortical microvascular density. Following focal cerebral ischemia, edema, but not infarct size, was less in transgenic mice relative to wild type littermates. This effect might be due to a reduction in the blood brain barrier breakdown, as confirmed by a decrease in Evans Blue leakage in the early post-ischemic phase. We conclude that angptl1 may have a beneficial role in the preservation of vascular integrity following focal cerebral ischemia.
Little is known of angptl1’s potential role in other processes. To identify the expression pattern and possible role of angptl1 during embryogenesis, we used gene targeting to generate angptl1 deficient, nLacZ knock-in mice. Staining for ß-galactosidase from embryonic day 9.5 to 6 months of age revealed that angptl1 was initially expressed in the paraxial mesoderm. Expression then shifted to intermuscular connective tissue (fascial plane), joint capsules and perichondrium (laryngo-trachea, ribs and long bones) but not the muscles. The vasculature, central and peripheral nervous systems, digestive, respiratory and other major organ systems did not show any angptl1 expression. This expression pattern suggests that angptl1 is related to development of the connective tissue and cartilage. Lack of phenotype in mutant mice may be due to a functional redundancy from other related factors.
In an attempt to know the role of adenosine A1 receptor in cerebral ischemia, the present study employed the ligation of bilateral carotid arteries to induce ischemia in Wistar rats. Changes of gene expression of adenosine A1 receptor in cerebral cortex of ischemic rats were compared with normal sham control and reperfusion group that received regular blood flow after a transient ischemia. The mRNA level of adenosine A1 receptor in cerebral cortex was markedly raised by this artificial ischemia. Also, reperfusion reversed this elevation to a level near the control. This change was also observed at the protein level using Western blot analysis of adenosine A1 receptor. The raised protein level of adenosine A1 receptor by ischemia was reversed to normal level after reperfusion. These data suggest that the gene expression of adenosine A1 receptor was increased by ischemia probably due to the compensative response of brain. The raised adenosine A1 receptor may play a protective role in these damaged tissues.
Subjects
缺血性腦中風
血管生成素相似蛋白1
腺甘酸
Stroke
Angptl1
Adenosine
Type
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