Pleiotrophin is a major regulator of the catecholamine biosynthesis pathway in mouse aorta

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 identified a dramatic upregulation of expression of tyrosine hydroxylase (TH), DOPA decarboxylase, and dopamine beta-hydroxylase in aortae of Ptn-/- mice in comparison with WT (Ptn +/+) mice. In contrast, transcripts of phenylethanolamine-N-methyltransferase, the enzyme catalyzing the conversion of norepinephrine into epinephrine, were not detected in aortae in either mouse strain. These findings suggest that Ptn gene expression has a critical role in determining the levels of expression of the enzymes of catecholamine biosynthesis in aorta and through this mechanism, PTN may regulate levels of endogenous catecholamine synthesis and potentially the vascular tone of aorta. (C) 2004 Elsevier Inc. All rights reserved.