Endothelial cell diversity revealed by global expression profiling

Abstract

The vascular system is locally specialized to accommodate widely varying blood flow and pressure and the distinct needs of individual tissues. The endothelial cells (ECs) that line the lumens of blood and lymphatic vessels play an integral role in the regional specialization of vascular structure and physiology. However, our understanding of EC diversity is limited. To explore EC specialization on a global scale, we used DNA microarrays to determine the expression profile of 53 cultured ECs. We found that ECs from different blood vessels and microvascular ECs from different tissues have distinct and characteristic gene expression profiles. Pervasive differences in gene expression patterns distinguish the ECs of large vessels from microvascular ECs. We identified groups of genes characteristic of arterial and venous endothelium. Hey2, the human homologue of the zebrafish gene gridlock, was selectively expressed in arterial ECs and induced the expression of several arterial-specific genes. Several genes critical in the establishment of left͞right asymmetry were expressed preferentially in venous ECs, suggesting coordination between vascular differentiation and body plan development. Tissue-specific expression patterns in different tissue microvascular ECs suggest they are distinct differentiated cell types that play roles in the local physiology of their respective organs and tissues.

Estradiol, acting through estrogen receptor alpha, restores dimethylarginine dimethylaminohydrolase activity and nitric oxide production in oxLDL-treated human arterial endothelial cells

“…In spite of HUVEC are often used to study endothelial mechanisms, experiments were developed in HUAEC in an attempt to determine if those genetic differences could alter the response to estradiol and to atherogenic compounds like oxLDL. Despite their common developmental origins, endothelial cells are not identical, differing widely in morphology and function, and existing different genes expressed specifically by the endothelium of arteries (Chi et al, 2003). Fetal circulation is rather different from adult as gas exchange does not occur in the lungs but in the placenta.…”

“…In spite of umbilical arteries carry deoxygenated blood at relatively low blood pressure, some evidences have shown that the specification of arterial and venous identity is largely genetically determined (dela Paz and D'Amore, 2009). In fact, phylogenetic approaches show the identity of umbilical arteries to different arteries in the body and the same occurs with veins (Chi et al, 2003).…”

“…Despite their common developmental origins, venous and arterial endothelial cells are not identical, differing widely in morphology and function. (Chi et al, 2003;Sobrino et al, 2009;dela Paz and D'Amore, 2009). Moreover, in the case of endothelial cells cultured from umbilical cord, it must take into account that in the umbilical circulation, the vein carries the oxygenated blood while the arteries carry the deoxygenated blood.…”

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis

“…A high degree of heterogeneity has been observed for endothelial cells isolated from different tissues and/or animal species. Also, significant differences exist between large-vessel and microvascular endothelium [13][14][15]. Nevertheless, the bulk of experimental evidence indicate that different members of the FGF family, mostly FGF1 and FGF2, can induce in vitro a complex ''proangiogenic phenotype'' in endothelial cells ( Fig.…”

ZD6126 inhibits orthotopic growth and peritoneal carcinomatosis in a mouse model of human gastric cancer

“…ZD6126 has significant antitumour effects in a wide range of histologically distinct subcutaneous tumour xenografts in nude mice . However, the efficacy of ZD6126 has not been examined at orthotopic sites where the endothelia are phenotypically distinct and tumour growth is likely to be more physiologically relevant to human disease (Craig et al, 1998;Chi et al, 2003).…”