Vascular Genomics of the Human Brain

Abstract

The microvasculature of the human brain plays an important role in the development and maintenance of the central nervous system and in the pathogenesis of brain diseases, and is the site of differential gene expression within the brain. However, human brain microvascular-specific genes may not be detected in whole-brain gene microarray because the volume of the brain microvascular endothelium is relatively small (0.1%) compared with the whole brain. Therefore, the differential gene expression within the human brain microvasculature was evaluated using suppression subtractive hybridization with RNA isolated from human brain microvessels. Gene identification was restricted to the first 71 clones that were differentially expressed at the brain microvasculature. Twenty of these were genes encoding proteins with known function that were involved in angiogenesis, neurogenesis, molecular transport, and maintenance of endothelial tight junctions or the cytoskeleton. Eighteen genes coding for proteins of an unknown function were identified, including five genes containing satellite DNA sequences. The results provide the initial outline of the genomics of the human brain microvasculature, and have implications for the identification of both targets for brain-specific drug transport and changes in microvascular gene expression in brain diseases.