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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:231.)
© 2002 American Heart Association, Inc.

Vascular Biology

Identification of a Zinc Finger Homoeodomain Enhancer Protein After AT₂ Receptor Stimulation by Differential mRNA Display

Monika Stoll; Alfred W.A. Hahn; Uwe Jonas; Yi Zhao; Bernhard Schieffer; Jens W. Fischer; Thomas Unger

From the Department of Physiology (M.S.), Medical College of Wisconsin, Milwaukee; Knoll AG (A.W.A.H., U.J.), Ludwigshafen, Germany; Department of Cardiology (B.S.), Medizinische Hochschule Hannover; and Institute of Pharmacology (M.S., Y.Z., J.W.F., T.U.), Christian-Albrechts-University Kiel, Kiel, Germany.

Address correspondence to Monika Stoll, PhD, Institute of Pharmacology, Christian-Albrechts-University Kiel, Hospitalstr 4, D-24105 Kiel, Germany. E-mail stoll{at}pharmakologie.uni-kiel.de

Using differential mRNA display, we isolated differentially expressed genes after stimulation of angiotensin II (Ang II) type 2 (AT₂) receptors in PC12w cells. Among the polymerase chain reaction products isolated, we identified Zfhep, a zinc finger homoeodomain enhancer–binding protein and the angiotensin AT₂ receptor itself, both implicated in developmental processes. In the presence of epidermal growth factor (EGF) a concordant expression pattern of Zfhep and AT₂ mRNA was observed with marked downregulation 6 hours after stimulation with EGF+Ang II. In quiescent PC12w cells, Zfhep mRNA was time-dependently induced by Ang II (10^-7 mol/L) up to 3 hours, an effect that was blocked by the selective AT₂ antagonist PD123177 (10^-6 mol/L). We extended our studies on Zfhep mRNA expression to cells of vascular origin (coronary endothelial cells [CECs]), that express AT₁ and AT₂ receptors, and that respond differently to Ang II dependent on which receptor subtype is stimulated. In CECs, Zfhep mRNA expression was induced up to 3 hours after AT₂ stimulation. Interestingly, this Zfhep induction was observed only when the AT₁ receptor was blocked by using the selective AT₁ receptor antagonist, losartan (10^-5 mol/L), suggesting a negative-regulatory influence of AT₁ receptors on AT₂-induced Zfhep mRNA induction. In conclusion, Zfhep not only represents a suitable marker for AT₂ receptor activation, but it may also link AT₂ signaling and downstream events involved in the proposed function of the AT₂ receptor in development and regeneration.

Key Words: angiotensin II • Zfhep • differential mRNA display • angiotensin receptors

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