To better understand the phenotype of pleiotrophin (PTN the protein, Ptn the gene) genetically deficient mice (Ptn -/-), we compared the transcriptional profiles of aortae obtained from Ptn -/- and wild type (WT, Ptn +/+) mice using a 14,400 gene microarray chip (Affymetrix) and confirmed the analysis of relevant genes by real time RT-PCR. We found striking alterations in expression levels of different genes of the renin-angiotensin system of Ptn -/- mice relative to WT (Ptn +/+) mice. The mRNA levels of the angiotensin converting enzyme (ACE) were significantly decreased in Ptn -/- mice whereas the mRNA levels of the angiotensin II type I (ATI) and angiotensin II type 2 (AT2) receptors were significantly increased in Ptn -/- mice when they were compared with mRNA levels in WT (Ptn +/+) mice aortae. These data demonstrate for the first time that the levels of expression of the Ptn gene markedly influence expression levels of the genes encoding the key proteins of the renin-angiotensin system in mouse aorta and suggest the tentative conclusion that levels of Ptn gene expression have the potential to critically regulate the downstream activities of angiotensin II, through the regulation of its synthesis by ACE and its receptor mediated functions through regulation of both the ATI and AT2 receptors. (C) 2004 Published by Elsevier Inc.