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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1469.)
© 2008 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Identification of a Core Set of 58 Gene Transcripts With Broad and Specific Expression in the Microvasculature

Elisabet Wallgard; Erik Larsson; Liqun He; Mats Hellström; Annika Armulik; Maya H. Nisancioglu; Guillem Genove; Per Lindahl; Christer Betsholtz

From the Department of Medical Biochemistry and Biophysics, Division of Matrix Biology (E.W., L.H., M.H., A.A., M.H.N., G.G., C.B.), Karolinska Institutet, Stockholm, Sweden; and the Wallenberg Laboratory of Cardiovascular Research (E.L., P.L.), Sahlgrenska University Hospital, Göteborg, Sweden.

Correspondence to Christer Betsholtz, Scheeles väg 2, A3, floor 4, SE-171 77, Stockholm, Sweden. E-mail christer.betsholtz{at}ki.se

Objective— Pathological angiogenesis is an integral component of many diseases. Antiangiogenesis and vascular targeting are therefore promising new therapeutic principles. However, few endothelial-specific putative drug targets have been identified, and information is still limited about endothelial-specific molecular processes. Here we aimed at determining the endothelial cell-specific core transcriptome in vivo.

Methods and Results— Analysis of publicly available microarray data identified a mixed vascular/lung cluster of 132 genes that correlated with known endothelial markers. Filtering against kidney glomerular/nonglomerular and brain vascular/nonvascular microarray profiles separated contaminating lung markers, leaving 58 genes with broad and specific microvascular expression. More than half of these have not previously been linked to endothelial functions or studied in detail before. The endothelial cell-specific expression of a selected subset of these, Eltd1, Gpr116, Ramp2, Slc9a3r2, Slc43a3, Rasip1, and NM_023516, was confirmed by real-time quantitative polymerase chain reaction and/or immunohistochemistry.

Conclusions— We have used a combination of publicly available and own microarray data to identify 58 gene transcripts with broad yet specific expression in microvascular endothelium. Most of these have unknown functions, but many of them are predicted to be cell surface expressed or implicated in cell signaling processes and should therefore be explored as putative microvascular drug targets.

Key Words: angiogenesis • endothelium • genomics • VEGF

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